Wednesday, March 30, 2016

Validation & its importance in Pharma

 What is validation?

GMP-definition is the validation of "establishing documented evidence that establishes a high degree of certainty that a particular process will consistently a product that provides the previously established specifications and quality attributes are available."
Appropriate and complete documentation is recognized as crucial for the validation. Standard Operating Procedures (SOP), production formulas, detailed documentation batch change Control, experimental reporting systems, analytical documents, reports development, validation protocols and reports are an integral part of validation philosophy. The validation of the documentation provides a source of information for the ongoing operation of the plant and is a resource that is used in the subsequent process of development or modification activities.
All test activities will take a level of impact assessment to ensure that systems, services andProducts were determined directly affected by the test.
A re-validation program should be implemented on a permanent equipment on the revalidation requirements and change control.

Types of Validation

1. Prospective validation
Establishing documented evidence that a device / process or system to do what they do, on a pre-planned series of scientific investigations within the meaning of validation sets basedPlan.

2.Concurrent validation
Is used when an existing process can be shown to be in a state of control by use of tests on samples taken at strategic points in a process, and at the end of the process. All data are collected simultaneously with the implementation of the process, to demonstrate sufficient information to process reproducibility.

3. Retrospective Validation
Establishing documented evidence that a process does not what it purports to do, based on review and analysis of historical data.

4. Design Qualification (DQ)
The intent of the DQ is in the planning and commissioning process met with a number of mechanisms, including:
- Generation of User Requirement Specifications
- Verification of this type corresponding user requirement specifications.
- Supplier Evaluation / Audit
- Check the Challenge of the design by GMP audits
- Product Quality Impact Assessment
- Specifying Validation documentation requirements of suppliers
- Agreements with the suppliers about the performance targets
- Factory Acceptance Test (FAT), Site Acceptance Test (SAT) and commissioning procedures
- Definition of construction and installation documentation) to assist with Installation Qualification (IQ.

  • Installation Qualification (IQ)
IQ is a proof that the equipment or system has been documented in developed delivered and installed in accordance with design drawings, vendor recommendations and in-house requirements. Moreover, IQ, that a record of the main features of the equipment or system is installed, how available and ensure that they are supported by sufficient and appropriate documentation to implement satisfactory operation, maintenance and control of changes.
  • Operational Qualification (OQ)
OQ is documented proof that operates the facility as provided in the above design, operation or approved acceptance range of equipment, as applicable. In cases where process steps are considered an appropriate placebo batch is used to demonstrate device functionality.
All new devices should be fully taken into service before the start of O.Q to ensure that at least be sure to use the device, complete with all mechanical assembly and pre-qualification checks are that the device is fully functional and that Documentation is complete.

  • Performance Qualification (PQ)
The goal of PQ is documented proof that the equipment can always be achieved while producing the specifications for a longer period at a defined operating point, a product of the specified quality. The specification will make reference to process parameters, in-process and product specifications. PQ requires three product batches available for all acceptance Criteria for in-process and product testing. For supply PQ requires the benefits of medium to fulfill all the data over a longer period of sampling.
The PQ documentation should be on standard manufacturing procedures and batch records and describe the methodology of sampling and testing to be.

What is Validated??

  • Basic
All process steps, production equipment, systems and environment, directly relevant to the production ofsterile and non-sterile products must be formally confirmed.
All major packaging equipment and processes should be validated. This validation is less comprehensive.
All ancillary systems, which should have no direct effect on product quality to be qualified by a technical documentation on the extent of the system and how it works.

  • Facility
- Manufacturing Area Design.
- Personnel and material flow, etc.


  • Process Equipment and Design
Process steps and equipment description. Ie dosing, formulation, packaging, washing equipment
and cleaning. etc


  • Utility Systems Design
Raw / steam cleaned, purified water, compressed air, air conditioning, vacuum, power, lighting, cooling water, waste water, etc.

  • Computerized Systems Design
Information system, automated laboratory equipment, automated manufacturing equipment, electronic records etc

  • Cleaning validation (CV)
CV provides evidence documenting that a cleaning procedure for the reduction of effective pre-defined maximum allowable limits, all chemical and microbiological contamination by one piece of equipment or a production area for processing. The means for evaluating the effectiveness of cleaning includes cleaning and disinfecting surfaces, sampling and inspection of product residues, cleaning residues and bacteria Contamination.
The term CV is used to describe the analytical investigation of a cleaning or by bicycle. The validation protocol should be based on background documentation on the reasons for the "worst case" test, where it is proposed. It should also develop the criteria for acceptance, including chemical and microbiological specifications, limits of detection and the selection of sampling.

  • Method Validation (MV)
MV provides documented evidence that the internally-developed test methods are accurate, robust, efficient, reproducible and repeatable. The validation protocol should be based on background documentation on the reasons for determining the method detection limit and sensitivity.

  • Computer Validation

Computer Validation is a proof to ensure systems are consistently documented in accordance with the predetermined specifications and quality function Attributes throughout their life cycle. Important aspects of this approach are) the validation of formal management design (through a specification process), system quality (through systematic review and testing, risk (through the identification and evaluation of new and critical functions) and life cycle (through sustainable change Control).
If the equipment in embedded computer systems, the elements of the validation of computer controlled, can be carried out as part of the equipment IQ and OQ Protocols.

Monday, March 28, 2016

क्या आप भी ऑफिस फ़्लर्ट से परेशान है ?

वर्क-लाइफ में हमें तरह तरह के लोग मिलते है , और हर वर्क प्लेस में हर प्रकार के लोग होते है जिनमे सरल, शांत और ज्यादा न बोलने वाले होते है तो  वहीं कुछ मुंहफट, दिलफेंक और फ्लर्ट मारने वाले भी होते है , दूसरे शब्दों में कहें तो जो अपनी प्यार की दुकान कहीं भी खोल के  बैठ जाते है , इनका दिल बड़ी जल्दी किसी पर आ जाता है और ये उसे अपनी हरकतों से परेशान करने से भी बाज नहीं आते।
इस लेख में हम आपको कुछ ऐसे टिप्स बता रहे है जिनको अपना कर आप ऐसे चिपकू टाइप लोगो से बच सकते है।
  1.  अपनी बॉडी लैंग्वेज पर ध्यान दें : –
आपको अपने हाव भाव यानि बॉडी लैंग्वेज पर विशेष ध्यान देना चाहिए , जब भी इस तरह के लोग कुछ परेशान करने वाली हरकत करें तो आपको अपनी बॉडी लैंग्वेज यानि अपने रिएक्शन पर विशेष ध्यान देना चाहिए , आपको ऐसे लोगो को नॉन रेस्पॉन्सिव टाइप सन्देश देना चाहिए।   ताकि उनकी  हरकतों को बढ़ावा न मिले
  1. पीछा छुड़ाने के चक्कर में हाँ में हाँ न मिलाये ..
  2. अक्सर इस तरह के लोग (लड़का /लड़की ) मौसम या कुछ ऐसे कॉमन विषय को लेकर आपसे बात की शुरुआत कर सकते है तो आपको चाहिए की इन लोगो की इस तरह की चिकनी चुपड़ी बातों से बचे , और साफ सुथरा , प्रोफेशनल ढंग अपनाएं।  और अगर लगे की सामने वाला ज्यादा चिपक रहा है तो उसे स्पष्ट शब्दों में इस तरह की बात न करने की हिदायत दे दें।
    1. अपनी ड्रेस का चुनाव अपने प्रोफाइल के अनुकूल करें …
    आपके कपडे आपके व्यक्तित्व को दर्शाते है , ऑफिस या वर्क प्लेस की ड्रेस का चुनाव बड़े ढंग से करें ताकि आपको बेवजह की पीठ पीछे की कानाफूसी का सामना न करना पड़े , कई बार हम कुछ ऐसे ड्रेस का चुनाव करते है जिससे सामने वाले को लग सकता है आप बहुत स्वछन्द है , बुराई ड्रेस में नहीं सामने वाले की सोच में हो सकती है , पर आप किसी की सोच को एक दम से नहीं बदल सकते , इस लिए खुद सावधान रहें तो बेहतर है।
    4 .  अपने कलीग से बात करें…
    कई बार आपकी चुप्पी को सामने वाला आपका सहयोग भी समझ सकता है तो किसी भी अवांछित स्थिति से बचने के लिए अपने सहकर्मियों से उसकी इस तरह  की हरकत का जिक्र जरूर करें ,और उस फ़्लर्ट कर रहे शख्श को अपना सन्देश उस दोस्त या सहकर्मी के जरिये जरूर पहुंचा दें की आपको यह सब पसंद नहीं और वह अपनी हरकतें बंद कर दे।
    5 . ऐसे लोगो से सोशल नेटवर्क या ईमेल पर कुछ भी अन ऑफिसियल बात न करें …
    ऐसा कई बार होता है कि सामने वाला  आपको ऐसे मेल करेगा/करेगी, ऐसे संदेश भेजेगा/भेजेगी कि जैसे वह आप पर जान छिड़कता/छिड़कती हो. वो आपको सोशल नेटवर्किंग की  साइट्स  फेसबुक, व्हाट्सएप पर भी अप्रोच करने की कोशिश करेगा/करेगी. उनसे बेहद सतर्क रहने की ज़रूरत है. दफ्तर के रोमांस के मामले में बचकर रहें क्योंकि यह अक्सर फंसाने का काम ही करता है।
    6. विरोध करें  ……
    हमें अपनी सुरक्षा का पूरा अधिकार है , हम ऐसे समाज में रहते है जहाँ हम अपने ढंग से जीने के लिए स्वतंत्र है ,जब                  आपको लगे की आप इस समस्या को अपने ढंग से हैंडल नहीं कर पा रहें तो इसे अपने बड़े अधिकारीयों की जानकारी में            लाएं।

    Note: आप इस तरह के लोगो को नहीं बदल सकते ये हर जगह मिल जाते है , बस आपको अपने खुद पर नियंत्रण रखना है।

Sunday, March 27, 2016

Interview Question for QC & QA


  • 1 Can any deviation be changed into the change control?
  • 2 What is the difference between Humidity and Relative Humidity?
  • 3 What should be the temperature and humidity for the tablet compression?
  • 4 What is the difference of vacuum pressure and vapor pressure?
  • 5 In Stability testing if significant change occurs then what will be the action plan?
  • 6 What do you mean by MKT (Mean Kinetic Temperature) in stability?
  • 7 What are the stability zones and stability conditions?
  • 8 What do you mean by Bracketing and Matrixing in stability?
  • 9 How to select HPLC column for a particular product?
  • 10 What is the composition of a C18 column?
  • 11 What is validation, validation protocol and validation master plan?
  • 12 What is the process validation?
  • 13 What is limit of cleaning validation?
  • 14 What do you mean by MACO?
  • 15 What is NOEL?
  • 16 What is recovery factor?
  • 17 How much the minimum recovery should be in swab sampling?
  • 18 What is the acceptance criterion for detergent washing?
  • 19 What do you mean by LOD and water content?
  • 20 What is the difference between LOD and water content?
  • 21 What is the difference between Calibration & Validation?
  • 22 What is the difference between Validation & Qualification?
  • 23 What is the disintegration time of coated tablets?
  • 24 What is the limit for friability of tablets?
  • 25 What is disintegration time for dispersible tablets?
  • 26 What do you mean by Q+5 in dissolution?
  • 27 What is the disintegration time for Hard Gelatin Capsule?
  • 28 What is limit of disintegration for Enteric coated tablets?
  • 29 What should be the sampling point in dissolution test?
  • 30 Which will give more drug release paddle or basket in dissolution?
  • 31 Tablets of which drug are used in dissolution calibration?
  • 32 What is the difference between Drug Purity and Drug Potency?
  • 33 What should be the minimum limit of a working standard?
  • 34 What is the storage condition for reference standard?
  • 35 How impurity is analyzed in any tablet?
  • 36 Why we use the placebo in analysis?
  • 37 What is the procedure to prepare the placebo?
  • 38 What is difference between method validation and method verification?
  • 39 What is the technology transfer and how is it done?
  • 40 What are the steps for the sterilization procedure for Dry Powder injection facility (from Starting)?
  • 41 What exepients are used in dry powder injections?
  • 42 What should be the LOD of dry syrup?
  • 43 How can you fix the known and unknown impurity limit for any drug substance?
  • 44 What is the relative response factor in related substances?
  • 45 How do we choose HPLC or Gas chromatography for a sample analysis?
  • 46 Why 3X sampling plan are implemented in process validation?
  • 47 What is the difference between temporary change control and deviation?
  • 48 Why we use toluene for resolution in UV calibration?
  • 49 What is photo stability?
  • 50 What is pooled sample and why it is required in dissolution test?
  • 51 Why we use disodium tartare for determination of factor in karl ficher titration?
  • 52 What are closely monitor parameters in stability study?
  • 53 What are the limits for LOD and LOQ?
  • 54 Why should we not dispatch the reprocess material to export?
  • 55 What is the formula for KF standardization?
  • 56 How we fix the validity period of a volumetric solution and re-standardization due date?
  • 57 How quantitative stability studies are done?
  • 58 What do you mean by CAPA?
  • 59 In KF Standardization why we use Disodium Tartarate?
  • 60 What is the difference between Deviation and Out of Specification?
  • 61 What is the difference between mix-up and cross-contamination?
  • 62 What is GMP, cGMP and GLP?
  • 63 What is the calibration of HPLC?
  • 64 How polarimeter is calibrated?
  • 65 What is the difference between Analytical method validation and Analytical method transfer?
  • 66 How melting point apparatus is calibrated?
  • 67 What is the difference between polarimeter lamp and IR lamp?
  • 68 What is the difference between sonication and homozinization?
  • 69 What is the difference between uniformity of content and content uniformity as official test for all tablets?
  • 70 What is limit of uniformity of content as per USP?
  • 71 How related substance method is developed for new compound which is not official in the pharmacopeia?
  • 72 If calibration of 12 bowl dissolution apparatus does not meets single stage procedure, how can you precede calibration?
  • 73 What is capacity factor?
  • 74 How will you calculate telling in any HPLC peak?
  • 75 What do you mean by end capping?
  • 76 What is the wave length of polarimeter lamp?
  • 77 Which gases are used in gas chromatography?
  • 78 Which gas is used as a mobile phase in GC?
  • 79 What types of columns are used in GC?
  • 80 What is stationary phase?
  • 81 What is hold time period for swab samples?

Saturday, March 26, 2016

what is the principle of AWC (Auto weight control) in compression machine.

AWC work on the principal of Compression force. In this first we set the machine on lower fill weight against the standard limit of the product and observe the avg. compression force. Similarly set the machine for higher fill weight and observe the avg. compression force.
Now set the target fill weight and run the machne, acquire the reference value of force at deiced parameter. Now feed the value of higher and lower compression force as observed above. 

Friday, March 25, 2016

Why we use Ion Exchange resins in watersystem?

Water purification is a necessary process for the water used in pharmaceutical manufacturing because it contains a lot of suspended material as well as in the form of ions. Turbidity and suspended solids can be removed by activated carbon filter but ions cannot be removed by ACF. This form of ions is called hardness of water. Hardness is denoted by Calcium and Magnesium ions. The process to remove this hardness is called softening and water is known as soft water.
Some resins are required to remove this hardness. Generally ion exchange resins are used for the process. These ions of hardness are taken by the resin. The resins are charged by chemicals to release this hardness.

Ion exchange resins are white to yellow colored synthetic polymers beads of small size ranging from 0.5-1.0 mm having the pores on their surface to trap and release the ions easily. Important – Resins are solids but measured in liter.

Two types of ion exchange resins are used in water systems - cation-exchange resins which release the hydrogen ions in water while trapping the ions from water and anion-exchange resins those release OH ions in exchange of hardness ions. Thus sodium ions are released in water and calcium and magnesium ions are attached with the resins. So the resins are required to regenerate before use again.

Anion is the negatively charged ion and anion exchanger is regenerated by 10-15% NaOH solution and water released from anion bed has pH between 7.5 and 9.5. Cation is positively charged ion and anion bed is regenerated by 8-12 % hydrochloric acid solution and pH of water released from the anion bed remains between 2 and 3.

By the process of regeneration sodium ions are attached again with the surface of ion exchange resin to get replaced by the calcium and magnesium ions of hard water.

Tuesday, March 22, 2016

Tips for resign from a job

Resigning from a job is something that most of us will have to face at some point in our careers – and there’s a right way and a wrong way to do it. If you’re thinking about quitting your job, here’s our best-practice guide to help you decide when to resign and how to resign.

BEFORE SUBMITTING YOUR RESIGNATION LETTER

  • Be 100% sure you’re ready to resign

    If you’re unhappy at work and it’s starting to affect your productivity and attitude, it may be time to reflect on whether it’s time to move on. But resigning is not something you should undertake hastily or impulsively.
    Take your time and weigh up the pros and cons before deciding to resign. Avoid a knee-jerk reaction you might regret later, especially if you don’t have another job to walk into. If you’re feeling dissatisfied, ask yourself whether your current role could be improved enough for you to stay on – or if there’s another, better role available in the same company. Consider a meeting with your manager, to see if they’re able to address your issues and make changes that could encourage you to stay.
  • Check your legal requirements

    If you’re convinced it’s the right time to jump ship, first look into your legal requirements. How much notice are you required to give? Are there any ‘no competition’ clauses in your contract? Read the fine print in your contract and make sure you’ve covered off any legal obligations.

RESIGNATION CHECKLIST & TIPS

  • Write an official resignation letter

    Make your resignation official with a short, straightforward letter. Email or hand it directly to your supervisor/line manager, and also give a copy to your company’s HR department.
  • Offer feedback if requested

    Your company may ask for feedback from you, often in the form of an exit interview. This is a good opportunity for you to provide constructive feedback after resigning – but avoid the temptation to be overly negative, as this will only make you appear unprofessional. It’s good form to thank your employer for the opportunity and experience they provided.
  • Retain a good work ethic

    The end may be in sight – but you’ll leave a better lasting impression if you remain as dedicated and hard-working as the day you started. Avoid the temptation to ‘check out’ prematurely – your boss will thank you for it. Unprofessional conduct might come back to haunt you, especially in a world that is increasingly connected. You don’t want a poor reputation to precede you in your next job or interview.
  • Prepare a comprehensive handover

    In addition to finishing projects, tying up loose ends, organising files and letting relevant stakeholders know who to contact once you’ve left, it’s generally expected that you will prepare a comprehensive handover for your replacement. This way, anyone who is required to take over your tasks will be able to do so with relative ease. Leaving incomplete or perfunctory handover notes will only demonstrate your lack of professionalism and care.
  • Parting words

    Say a final ‘goodbye’, whether it’s emailed around the company or announced at a gathering on your last day. Thank your employer and colleagues for the opportunity to work with them. Again, you’ll be best remembered by how you present yourself in your final moments, so make an effort and leave with your head held high.

HOW TO RESIGN: DOS & DON’TS

DON’T resign too hastily – especially if you don’t have another job lined up. Remember, it can take three to six months to find a new job and you may not be eligible for unemployment benefits if you quit. Remember the golden rule: it’s easier to find a job when you already have one!
DO leave your workplace as you found it. Remember to clean up the files on your computer, deleting any personal emails and organising files clearly for your successor (if appropriate). Clean your desk and take home any personal belongings.
DON’T brag about your new job. Be modest and discreet – even if you’re inwardly whooping for joy.
DO ask for a written reference that you can keep on file, in case you ever need it in the future. It’s much easier to get one before leaving, rather than coming back to your old boss at a later date

Monday, March 21, 2016

Do and Don'ts in interview

Job Interview Tips


Here are a few more do's and don'ts for being at your best during a job interview

Job Interview Do's:

Preparing for a job interview is essential to making a good impression. Employ these handy job interview techniques to win over your interviewer:
  • Plan to arrive on time or a few minutes early. Late arrival for a job interview is never excusable.
  • Greet the interviewer by their first name.
  • Wait until you are offered a chair before sitting. Sit upright and always look alert and interested. Be a good listener as well as a good talker. Smile!
  • Maintain eye contact.
  • Follow the interviewer's leads but try to get them to describe the position and duties early in the interview so you can relate your background and skills to the position.
  • Make sure you convey your good points factually and sincerely. Keep in mind that you alone can sell yourself to an interviewer. Make them realise why they need you in their organisation.
  • Always conduct yourself as if you are determined to get the job. Never close the door on an opportunity. It is better to be free to choose from a number of jobs rather than only one.

Job Interview Don'ts:

  • Answer questions with a simple 'yes' or 'no'. Use the CAR technique (Context, Action, Result) wherever possible. Share things about yourself relating to the position.
  • Lie. Always answer questions truthfully, frankly and as concisely as possible.
  • Ever make derogatory remarks about your present or former employers, colleagues or companies.
  • 'Over-answer' questions. The interviewer may steer the conversation into politics or economics. It is best to answer the questions honestly, saying no more than is necessary.
  • Let your discouragement show. If you get the impression the interview is not going well and you have already been rejected, don't show discouragement or alarm. Occasionally an interviewer who is genuinely interested in you may seem to discourage you in order to test your reaction.
  • Ask about salary, bonuses or holidays at the first interview - unless you are positive the employer is interested in hiring you and raises the issue first. However, know your market value and be prepared to specify your required salary or range.

Sunday, March 20, 2016

Difference between OOS & OOT


1. OOS (out of specification) is the comparison of one result versus a predetermined specification criteria while OOT (Out of Trend) is the comparison of many historical data values versus time.
2. OOS investigations focus on determining the truth about that one value while OOT investigations focus on understanding non-random changes.
Example:
The specification limit for assay is: 95.0-105.0 % w/w of label claim

Case-1: For a particular batch, the result obtained 94.2 % w/w -This result is out of the specification limit. This is called OOS.

Case-2: The result obtained 95.8 % w/w. Although the results are well within the specifications, we should compare the result with the previous batches trend. If we found the average value of the trend as 99.0 % w/w then this batch result (95.8 % w/w) is called out of trend.

Saturday, March 19, 2016

Drift in analytical balance and its importance

In the pharmaceutical industry and bioscience research field, many laboratories make use of analytical balances. The analytical balances used in the bioscience research and pharmaceutical industry are very sensitive. These balances can be heavily affected by the way the measuring personnel handle them and by the environment in which they are installed. The environment in the pharmaceutical laboratory needs to be assessed by running assessment tests. Based on the results of these assessments should be proposed concrete measures for improving the lab environment.



The weighing instruments in a pharmaceutical lab should always operate is quick and accurate. It should be avoided any events in the lab that would affect the analytical balance measurements results, such as opening and closing a breeze break door, for example. This is not an optimal way of conducting analytical balance weight measurements. When the breeze break door is open, the weighing area’s temperature will change because the air within the breeze break changes.

Analytical balances used in a pharmaceutical lab are used for extremely precise measurements, such as the microbalance capable of measuring 1 millionth of a gram, for instance. These highly accurate weighing instruments are used for quality control of the processes involved in the pharmaceutical industry manufacturing production.

Analytical Balance Drift

Sometimes a phenomenon called “drift” is experienced in the weighing instruments, including high precision analytical balances. This undesired phenomenon consists in measurements changing in one direction or displays becoming unstable with the passage of time. Unstable readings may occur with no weight applied or the weight readings do not stabilize due to the analytical balance drift effect. This can be explained by the static electricity accumulated due to the dry environment and friction from insulated material. 
The pharmaceutical production lines are having clean environments, controlled with 24 hour air conditioning. In such an area the humidity levels is often below 20 percent. By moving around objects in such a dry environment the friction causes building up of static electricity. Research has proved that people working in such a research lab or pharmaceutical production line can build up themselves around 10,000 volts of electricity. The effects of the static electricity become even greater under these circumstances and they can lead to errors of dozen milligrams.


Factors Affecting the Analytical Balance Drift

In order to avoid the static electricity build up and the apparition of the analytical balance drift effect, it would be necessary that the humidity level in the weighing instrument's installation environment to be increased over 40 percent. In case that the static electrical build up occurs faster than the electrical discharge, it is necessary to conduct weighing operations only after removing electrical charges from the weighing sample and to introduce a static eliminator. It should be avoided the use of plastic containers for the weighed items and the operators of the analytical balances should always stay on an anti-static floor covering.

Another environmental factor that can dramatically affect analytical balances stability is temperature. Temperature control is therefore imperative in avoiding the analytical balance drift phenomenon. This includes both the maintaining the constant temperature of the weighing instrument as well as controlling the room temperature. For the best temperature stability, the room should be constantly maintained whiting two temperature degrees variation, day and night. The weighing instrument should be always plugged in and turned on, in order to maintain its temperature constant as well. Generally balances have an error of 2 ppm/°C.

common Audit (483 observation and GMP) mistake

1. Wear personal protective equipment one common GMP mistake is not wearing your safety glasses. Your eyes are too precious not to protect them. Always wear your safety glasses, safety shoes, respirators, and other personal protective equipment. Take the time to think things through. Stay alert, and trust your instincts. Avoid situations that look potentially dangerous, and let your supervisors or others know. Read the Material Safety Data Sheets (MSDS) for all materials that you work with.
2. Read and observe all labels and signs. I once saw an experienced operator suspect that a vendor had changed the process on a raw material because the label "looked different" Read all labels and signs carefully. Check for "released" stickers. Ensure that the material has not expired and that its the correct material. Caution and warning signs in your plant should be printed in all languages spoken in the plant.
3. Be especially careful around breaks, when you are tired, called away, and so on. GMP and safety violations occur most often right before break times, before lunch, before your shift is over, when it's time to go home, when someone interrupts you or breaks your train of thought, and so on. Be especially vigilant during those times. The most common injuries in our business seem to be hand and back injuries, so use proper lifting techniques, slow down, and think about what you are about to do before putting your hands or back at risk.
4. Wear only appropriate clothing. In most companies, supervisors are responsible for providing on-the-job training (including training in proper attire, such as sterile gowning) and then monitoring employees to make sure that they are wearing appropriate clothing. One common GMP error is not wearing your lab coat while you are in the laboratory (or visitors or contractors not wearing hair coverings, shoe coverings, lab coats, and so on). Splashes can be dangerous and can ruin your clothes. When visiting bulk chemical plants, don't wear designer suits or shoes.
Another common error is wearing your lab coat or plant uniform outside the building. Some 483 observations noted that employees were smoking outside of buildings while wearing their plant uniforms. Some types of jewellery are not allowed in certain areas. Check with your supervisor if you're not sure.
5. Keep surfaces and equipment clean. Follow approved cleaning procedures, and use approved cleaning solutions, People have become sick and in the most serious case that I'm aware of, have died — because cleaning was inadequate, and the cleaning process had never been validated. One of the first things that investigators or visitors notice when they visit your plant is the facility's general cleanliness. Don't stack cardboard boxes in the hallways. Before you use a piece of equipment, ensure that it was cleaned by checking the "Cleaned Equipment" tag or the equipment logbook. If possible, open the equipment and look inside to make sure that no rinse water was accidentally left behind.
6. Wash your hands. Most pharmaceutical plants have signs in the bathrooms reminding employees to wash their hands before returning to the plant. If you've ever put your hand on a plate and cultured the bacteria present, you know that bacteria are everywhere, in large quantities, although omnipresent in life, they are not something that any one of us wants in our medicines or injectables.
7. Report an Illness. I know of no other industry-other than food - that requires personnel working over open product to notify their supervisors when they have a cold it is a GMP requirement that employees and temporary employees do this. On those days when you're not feeling up to par, you can be assigned to attend GMP classes, revise SOPs, or catch up on your scintillating GMP reading, such has articles like this one.
8. Use only released raw materials, packaging components, and labels. Use no expired materials. Under cGMPs, only released materials can be used in all clinical and commercial lots of product. A common error is to store expired materials with current materials. Remove, segregate, and/or destroy all expired materials.
9. Think. Even though the pace in our industry is fast, and everyone has more to do than they can possibly get done, everyone deserves the time to think things through.
Every time I have allowed myself to be rushed, I have made a critical mistake.
10. Always fill in the blanks. Record all requested information. If its truly not applicable, write N/A; your initials, and the date. If pages or sections of forms are not applicable, line through them, write N/A, your initials, and the date. The correct information must be entered on batch records, equipment logbooks, and test result forms, otherwise, your QA department will be checking with you soon to find out why you didn't complete the work.
11. Record results as you get them. One common GMP error is to speed through documents at the end of the day or at the end of your shift, filling in all the blanks at one time. But we all know that it is impossible to remember what we did five minutes ago, much less eight hours ago. You have to train yourself and your people to record results and information as you get it - on batch records, lab notebooks, and test result forms.
12. Use Indelible Ink. The industry standard is black indelible ink because it photocopies well and does not smear. Pencil is unacceptable because it smears easily and can be erased.
13. Banish the correction fluid. Using correction fluid is not allowed. I know of some employees who don't even have correction fluid in their desk drawers, to avoid the temptation to use it.
14. Line through, Initial, and date all changes. The correct way to make a change is to line through the error once using your indelible ink pen, clearly write the correction above or beside it, and initial and date the correction.
15. Never backdate or falsify records. Always use today's date when documenting your work. If you do not, you are falsifying records. For example, if I made a batch of a product today, and did not fill out a line on a batch record, a QA employee would stop by and ask me whether I had completed that step. If I did remember completing it, I would write in the Comments section of the document that QA had noticed that I had failed to document the step and that I had in fact completed it. I would initial and date my comment the day that I was writing it. Preferably, I would have an attachment or some sort of corroborating data to back this up! The better idea is to record data when you get it. Under no circumstances should you go back into a batch record and fill it out as though you had filled it out properly to begin with.
16. There is no such thing as a dumb question. Better to ask and get an answer than to assume and risk a batch, someone recently told me that a single gram of one of their active ingredients was worth $8,000. Some larger biotech companies with products on the market have batches worth $4-7 million each. An awful lot of money is riding on those batches, not to mention the safety, purity, and effectiveness of the products. It's critical that supervisors make sure their people feel comfortable asking those questions and admitting their mistakes.
17. Take action to make things better. In all of the classes I teach, I always ask people to take action to make things better.
Each of us sees things in our day-to-day jobs that others do not. Or we may reach a conclusion faster than someone else. Have the courage to bring up things that need to be improved. Be the responsible employee who picks the piece of paper from the floor rather than steps over it.
As your move up in your career, people are going to trust you with information that is confidential and sensitive. You must honour their confidences but also take action. For example, if employees confide in you that they are worried about the safety of their work area, you must immediately inform the area manager and also your Environmental Health & Safety department coordinator in writing. The point is to not assume that the charge is correct, but to turn it over to people who can follow up.
18. Ensure that equipment Is calibrated before using it. Equipment that must be calibrated in a manufacturing or laboratory environment typically has an equipment calibration tag on its front, side, or back that indicates the date the equipment was last calibrated, who did the calibration, and when the next calibration is due. Check to make sure that your equipment is within calibration before you use it. Otherwise, your results or measurements could be inaccurate.
19. Record ID, part, lot, document, revision, and other control numbers. When something goes wrong with a product lot, trying to determine the true source of the problem is often like solving a mystery. The GMPs require that you assign and use unique numbers on each lot of your raw materials, reagents, documents, and all lots of produced product to permit traceability should there ever be a problem.
So when filling out a batch record or recording your results, record equipment, lot, sample, reference sample, and document and revision numbers.
20. Do not bring food, gum, tobacco, or house plants into production and laboratory areas. A common GMP error is bringing drinks into a laboratory. Smoking, eating, and drinking are prohibited in a GMP area. You do not want to have food inside a GMP area because rodents and other pests will try to enter the f facility to get the food. A beetle can bore through 0.125 inch of solid plastic to get to food or the glucose or sucrose stored on pallets in your warehouse. Houseplants may have insects on their soil and leaves.
21. Check your pest control devices frequently. If you use an outside pest control service, test it by placing a plastic mouse in one of the traps. If the service doesn't find it, it's not doing a thorough job inspecting and cleaning the traps. Because rats like to run along walls - they do not see well, and they feel safer against a wall - rodent traps should be placed along walls. Clean the bottom tray of insect electrocutors frequently. You may have an insect infestation in the bottom of the tray. If a pregnant female is electrocuted, her young may survive to feed on the remains of the dead insects inside the tray.
22. Before signing anything, check for accuracy, for completeness, and correct calculations. In our industry, a signature is a legal and an ethical responsibility. If you have signature authority and are asked to sign something, you must, to the best of your ability, review it thoroughly and completely, make sure that everything that needs to be attached is attached, and make sure that all calculations are correct. Never sign something without thoroughly reviewing it first. Never sign something that you know to be wrong. Get it corrected and then sign it.
23. Print clearly in logs, and fill them out completely. Fill out all logs and other documents completely. Your handwriting must be clear and legible. If your handwriting, like mine, is difficult to read, then print.
24. Record data directly on the appropriate form or notebook. Do not write original data on scrap paper, napkins, or paper towels and then transfer the information to the appropriate form or notebook. If you accidentally record your data on a piece of scrap paper, staple it to the form or notebook, because it is original data. Always attach printouts and labels where indicated. Never throw away original data.
25. Never simply average out-of-specification results to obtain a passing result do not continue testing samples until you get enough that pass. As a result of the Barr case, there has been a lot of scrutiny in this area. Every company should have an SOP that discusses how to handle out-of- specification results and how to handle failure investigations. One executive recently told me that he suspects that analysts were not telling their supervisor when they got an out-of - specification result because an investigation would have to be done. Supervisors take note: Encourage your people to tell you when they get an unusual result, and don't punish them when they do.
26. Have another person perform double checks as Indicated In the batch record. Double checks are required for critical steps, like weighing and adding raw materials, because people have discovered that historically those are problematic areas. A double check means that one person performs the work while another person observes and makes any suggestions or corrections. Individuals then sign or initial the batch record where indicated. GMPs require that you have sufficient staff to do this.
27. Keep shipping, receiving, and other doors closed. A common error is to leave shipping and receiving doors open after a delivery has arrived - an open invitation for pests of all kinds. Owls, snakes, rats, and mice have been found in warehouses looking for food, water, and shelter. A field mouse only needs 0.25 inch to get under a door, so check the bottom of your outside doors. If there is a gap, you could be inviting a rodent problem. Many years ago a mouse ran across the back of a room in an older office building where I was teaching a GMP class. (He probably wanted to make sure he met his GMP training requirement.) The cGMPs require that you have an effective pest control program; keeping your receiving doors closed will help.
28. During an Inspection, answer all questions honestly and directly. Do not guess or speculate. Do not volunteer information. Refer questions that you cannot answer to your supervisor. FDA and other regulatory agencies know that this is how employees are trained. Don't be evasive, and don’t try to hide the truth. Don't guess, and don't state your opinion. "If you think we're bad, you should see those guys down the hall!"
29. Report mistakes - or suspected mistakes - as soon as possible to your supervisor. I hate to make mistakes, rather be perfect. But the truth is that we're all human, and human beings make mistakes. As a supervisor, encourage your people to tell you things. Don’t jump all over them when they do so they never do it again. And don't go looking for scapegoats. If something goes wrong in your group, you as a supervisor or manager must accept responsibility for the mistake see what you can reconstruct or recover, and figure out how you can prevent the mistake from happening again.
30. Read and become familiar with all SOPs and other documents that relate to your work. You must know your SOPs. A common 483 observation continues to be "Firm failed to follow its own SOP." If an SOP needs to be revised, tell your supervisor and offer to help revise it and get it approved