Thursday, June 30, 2016

21 CFR 11 Compliance Question and Answers?

Q: What are the requirements of 21 CFR 11?
A: 21 CFR 11 requires that closed computer systems must have a collection of technological and procedural controls to protect data within the system. Open computer systems must also include controls to ensure that all records are authentic, incorruptible, and (where applicable) confidential.

Q: What computer systems must be compliant with 21 CFR 11?
A: All computer systems which store data which is used to make Quality decisions or data which will be reported to the FDA must be compliant with 21 CFR 11. In laboratory situations, this includes any laboratory results used to determine quality, safety, strength, efficacy, or purity. In clinical environments, this includes all data to be reported as part of the clinical trial used to determine quality, safety, or efficacy. In manufacturing environments, this includes all decisions related to product release and product quality.

Q: What is computer system validation?
A: Validation is a systematic documentation of system requirements, combined with documented testing, demonstrating that the computer system meets the documented requirements. It is the first requirement identified in 21 CFR 11 for compliance. Validation requires that the System Owner maintain the collection of validation documents, including Requirement Specifications and Testing Protocols.

Q: What is accurate record generation?
A: Accurate record generation means that records entered into the system must be completely retrievable without unexpected alteration or unrecorded changes. This is generally tested by verifying that records entered into the system must be accurately displayed and accurately exported from the system.

Q: How must records be protected?
A: Electronic records must not be corrupted and must be readily accessible throughout the record retention period. This is usually performed through a combination of technological and procedural controls.

Q: What is limited system access?
A: System owners must demonstrate that they know who is accessing and altering their system data. When controlled technologically, this is commonly demonstrated by requiring all users have unique user IDs along with passwords to enter the system.

Q: What is an audit trail?
A: An audit trail is an internal log in a program that records all changes to system data. This is tested by demonstrating that all changes made to data are recorded to the audit trail.

Q: What are operational system checks?
A: Operational system checks enforce sequencing of critical system functionality. This is demonstrated by showing that business-defined workflows must be followed. For example, data must be entered before it can be reviewed.

Q: What are device checks?
A: Device checks are tests to ensure the validity of data inputs and operational instructions. Generally speaking, Ofni Systems does not suggest testing keyboards, mice, etc., because these input devices are implicitly tested throughout other testing. However, if particular input devices (optical scanners, laboratory equipment, etc.) these devices should be tested to ensure the accuracy of system inputs.

Q: What training requirements are required for 21 CFR 11 compliant programs?
A: Users must be documented to have the education, training, and experience to use the computer system. Typically training can be covered by your company training procedures.

Q: What is a policy of responsibility for using electronic signatures?
A: Users must state that they are aware that they are responsible for all data they enter or edit in a system. This can be accomplished technologically through accepting conditions upon signing into the system or procedurally by documenting this responsibility as part of training.

Q: What documentation requirements are required for 21 CFR 11 compliant programs?
A: Documentation must exist which defines system operations and maintenance. Typically these requirements are met by company document control procedures.

Q: What are the requirements for electronic signatures?
A: All electronic signatures must:

> Include the printed name of the signer, the date/time the signature was applied, and the meaning of the electronic signature.

> Be included in human readable form of the record. Electronic signatures must not be separable from their record.
> Must be unique to a single user and not used by anyone else.
> Can use biometrics to uniquely identify the user. If biometrics are not used, they need at least two distinct identifiers (for example, the user ID and a secret password).

Q: Does 21 CFR 11 have any requirements for passwords or identification codes?
A: Yes. Procedural controls should exists to ensure that:

> No two individuals have the same user ID and password.
> Passwords are periodically checked and expire.
> Loss management procedures exists to deauthorize lost, stolen, or missing passwords.

What is AHU (Air Handling unit)?

An air handler, or air handling unit (often abbreviated to AHU), is a device used to condition and circulate air as part of a heating, ventilating, and air-conditioning (HVAC) system. An air handler is usually a large metal box containing a blower, heating or cooling elements, filter racks or chambers, sound attenuators, and dampers. Air handlers usually connect to a ductwork ventilation system that distributes the conditioned air through the building and returns it to the AHU. Sometimes AHUs discharge (supply) and admit (return) air directly to and from the space served without ductwork.

Small air handlers, for local use, are called terminal units, and may only include an air filter, coil, and blower; these simple terminal units are called blower coils or fan coil units. A larger air handler that conditions 100% outside air, and no recirculated air, is known as a makeup air unit (MAU). An air handler designed for outdoor use, typically on roofs, is known as a packaged unit (PU) or rooftop unit (RTU).

The design, installation, commissioning and qualification of clean rooms heating, ventilation and air conditioning (HVAC) systems is often one of the largest considerations in the design of a new pharmaceutical or biotechnology manufacturing facility. With high running costs (energy associated with the movement, cooling and heating of air) and the potential to impact upon safety and product quality, getting them right
is important for business, safety and good manufacturing practice (GMP) criticality.

The design of the HVAC system will be based upon the clean room suite that it serves, and will be affected by factors such as the number of rooms served, the layout of the rooms, the equipment within the rooms and, most critically from a qualification perspective, the environmental conditions that the rooms must achieve.

The air handling unit helps maintain each room's clean environment by providing an appropriate volume of clean air to each room at the correct temperature and humidity.

The air is filtered by pleated paper filters called high efficiency particulate air (HEPA) filters which, depending upon the classification of the rooms, are located either within the air handling unit or where the air enters each room. Cooling and heating coils are also located within the air handling unit, increasing or decreasing the air temperature to ensure that the room temperatures remain within specification.

Reliable operation of the air handling unit within established limits is critical, not only to prevent product quality from
being compromised by poor air conditioning, but also for the following reasons:

- to prevent cross contamination of products to maintain operator safety,
- where the HVAC is being used for this purpose to maintain product safety,
- where the HVAC is being used for this purpose.

Defining the Requirements

The cost of change during a project, based on the stage of the project.
Whereas other services and utilities can be (relatively) easily moved within a building's framework once the building work has been completed, the HVAC is much more integral with the building's fabric, making retrospective modifications much more time consuming and expensive. Getting the specification and design right first time is very important.

What are the problems?

If the design phase is completed without considering the compliance aspects of the clean rooms, then there is a high likelihood of incurring significant time delays and costs during the validation period, as a result of having to make mechanical changes to the installation or revisiting some of
the commissioning work.

Some typical examples of areas where problems can occur as a result of not designing for compliance are highlighted below, together with suggested actions to try to avoid these problems from occurring.

Operating tolerances. Design, commissioning and validation criteria must be determined for GMP-critical parameters such as air change rates, room differential pressures, temperature and humidity. For example, different tolerances may need to be applied at commissioning and validation to ensure that the facility will operate reliably within the validation acceptance criteria limits.

Air filtration. The level of air filtration will vary depending upon the classification of the clean rooms being served. For example, an ISO Class 5 room (Class 100) will require terminal HEPA filters, whereas an ISO Class 8 environment (Class 100000) may be achieved by using a high-grade (non-HEPA) filter within the air handling unit. To avoid failures during validation integrity testing it is important for the validation and design teams to discuss the in situ test requirements, and to agree upon appropriate grades of air filtration.

What are the criteria for validation?

During AHU validation, following tests shall be carried out

Filter efficiency test,
Air velocity & number of air changes,
Air flow pattern (visualisation),
Differential pressure, temperature and RH,
Static condition area qualification,
Dynamic condition qualification,
Non-viable count,
Microbial monitoring,
Area recovery and power failure study.

Why re-validation need to be performed?

AHU system shall be revalidated periodically as mentioned in the regulatory standards. AHU shall be revalidated in following cases also.

When basic design of AHU is changed,
When clean room volume is changed,
When new equipment is installed,
When a construction is carried out, that calls for reconstruction of AHU system.

Friday, June 24, 2016

USP39-NF34 became official on 01 May 2016. Items of interest include

Apparatus for Tests and Assays
Chapter 21 Thermometers [This has been deleted]
Biological Tests and Assays
Chapter 162 Diphtheria Antitoxin Potency Testing for Human Immune Globulins [This is a new chapter]
An in vitro method is provided that is suitable for determining the potency of diphtheria antitoxin (antibodies against the diphtheria toxin) in preparations of plasma-derived human immune globulins. Diphtheria toxin is produced by Corynebacterium diphtheriae and has the ability to produce a cytopathogenic effect on susceptible epithelial cell lines. The test is based on the ability of diphtheria antitoxin to neutralize the diphtheria toxin, decreasing its cytotoxic effect. Specifically, the test determines the potency of the diphtheria antitoxin based on its ability to inhibit the cytotoxic effect of diphtheria toxin on cultured Vero cells (African green monkey kidney epithelial cells) relative to a reference standard. The mitochondrial dehydrogenases of live Vero cells can reduce the dye 3-4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) to a blue/black product that is then measured by absorbance at 540 nm. If no or little diphtheria antitoxin is present, then diphtheria toxin induces cell death and the inability of cells to reduce MTT, resulting in the presence of white or colorless wells. Acceptance criteria are defined by the appropriate regulatory agencies.
With the 1 st supplement (effective 1 st August 2016):
Chapter 87 Biological Reactivity Tests, In Vitro
Test Control and USP Reference Standards
Chemical Tests and Assays
Chapter 191 Identification Tests-General
Introduction, Chemical Identification Tests, and Instrumental Identification Tests
Chapter 507 Protein Determination Procedures [New chapter]
Physical Tests and Determinations
Chapter 791 pH
Introduction, Instrument Requirements, Buffer Solutions for Calibration of the pH Measurement System, Calibration, and Operation.
Chapter 1035 Biological Indicators for Sterilisation [Chapter deleted]
Chapters added:
1207 Package Integrity Evaluation- Sterile Products
1207.1 Package Integrity Testing in the Product Life Cycle – Test Method Selection and Validation
1207.2 Package Integrity Leak Test Technologies
1207.3 Package Seal Quality Test Technologies
1228 Depyrogenation
1228.1 Dry Heat Depyrogenation
1229.5 Biological Indicators for Sterilisation
1229.9 Physicochemical Integrators and Indicators for Sterilisation
1229.12 New Sterilisation Methods
Chapters deleted:
1209 Sterilisation- Chemical and Physicochemical Indicators and Integrators
With the 2 nd supplement (effective on 1 st December 2016):
General Information
1029 Good Documentation Guidelines{ New chapter]
1228.3 Depyrogenation by Filtration [New chapter]
1228.5 Endotoxin Indicators for Depyrogenation [New chapter]
1229.13 Sterilisation-in-Place [New chapter]
1231 Water for Pharmaceutical Purposes [revise chapter]

Wednesday, June 22, 2016

Different types of cheques in India

A cheque is a payment instrument that is issued by a bank account holder for making payments to an individual or company and cash withdrawals from the bank. Apart from that, it also facilitates funds transfer to another bank account. For instance, you can make cash payment for a utility bill or you can do it by writing a cheque. The biggest benefit of a cheque is that it allows high value transactions which may become a bit cumbersome if hard cash was used instead.


The following details are necessary in a cheque –

A cheque must be drawn upon a specified bank (Drawee).A cheque must be signed by the person (Drawer) issuing the cheque.A cheque must have the name of the recepient (Payee) of the cheque.A cheque must mention the amount of money in words and figures.A cheque must be dated.

Classification of Cheques:

A cheque is one of the safest modes of making payment as there is an entry against the cheque honoured by the bank that can be traced back if needed.

Based on the location, cheques are classified as: –

Local cheques:

If issued by a bank in the same city as the payee.

 Outstation cheques:

If a given city’s local cheque is presented elsewhere it becomes an outstation cheque and may attract some nominal but fixed banking charges.

 At par cheque:

is a cheque which is accepted at par at all its branches across the country. Unlike local cheque it can be present across the country without attracting additional banking charges.

Based on its value, cheques are classified as: –

Normal Value cheques:

Cheques below the amount of Rs. 1 lakh are called normal value cheques.

High Value cheques:

Cheque bearing an amount higher than Rs. 1 lakh is a high value cheque.

Gift cheques:

Cheques used for gifting money to loved ones are gift cheques. The value may vary from Rs. 100 to Rs. 10,000.

Cheques are mainly of four types:-

1) Open cheque:

A cheque is called open when it is possible to get cash over the counter at the bank. The holder of an open cheque can receive payment over the counter at the bank, deposit the cheque in his own account or pass it to someone else by signing on the back of a cheque.

2) Bearer cheque:

A cheque which is payable to any person who presents it for payment at the bank counter is called ‘Bearer cheque’. A bearer cheque can be transferred by mere delivery and requires no endorsement.

3) Order cheque:

It is the one which is payable to a particular person. In such a cheque the word ‘bearer’ may be cut out or cancelled and the word ‘order’ may be written. The payee can transfer an order cheque to someone else by signing his or her name on the back of it.

4) Crossed cheque:

When a cheque is crossed, the holder cannot encash it at the counter of the bank. The payment of such cheque is only credited to the bank account of the payee. Crossed cheque is done by drawing two parallel lines across top left corner of the cheque, with or without writing ‘Account payee’ in the space between the lines.

Banks also offer various cheques which guarantee payments.

A self cheque:

is written by the account holder as pay self to receive money in physical form from the branch where he holds his account. This can be alternated by using an ATM card.

Post-dated cheque (PDC):

A PDC is a form of a crossed or account payee bearer cheque but post-dated to meet the said financial payment at a future date. The cheque is valid from the date of issue to three months.

A Banker’s cheque:

A banker’s cheque is issued by a bank drawing money from its own funds rather than that from an account holder’s. Banker’s cheque is issued after the bank verifies the account status of the requestor and the amount is immediately deducted from the customer’s account.  A banker’s cheque cannot be dishonored as in the case of a normal cheque, when an account holder has insufficient funds in his/her account. Though different from a normal cheque it requires clearing too.

A Traveller’s cheque:

It is a printed open type cheque issued as an alternate for carrying around cash while travelling abroad or on a vacation to a foreign country as they come with a replacement guarantee and lifelong validity. Traveler’s cheques are widely accepted by merchants, restaurants and other recreational organizations. The unused cheques from the recent trip can be used for your next trip.

Friday, June 17, 2016

Growth Promotion Test of media

The purpose of the Growth Promotion Test is to determine the suitability of culture media. The medium is challenged with a small number of microorganisms to assure the nutritive properties. The test is described in USP Chapter <61>: Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests, USP Chapter <62>: Microbiological Examination of Nonsterile Products: Tests for Specified Substances and USP Chapter <71>: Sterility Tests.

We perform growth promotion testing (GPT) on solid media and broths according to Ph Eur and USP. The purpose of We perform growth promotion testing (GPT) on solid media and broths according to Ph Eur and USP. The purpose of the test is to ensure the quality and functionality of the media before using it for analysis. GPT should be performed on solid media and broths but not for dilution solutions and rinsing fluids.

GPT is performed by inoculating the product with ≤ 100 CFU of microorganisms, defined by the pharmacopoeia.  The test can be quantitative, at which 50 – 200% of the inoculated microorganisms should be recovered after incubation of the media, or it can be qualitative where the requirement is “growth” or “no growth”. GPT is described in Ph Eur 2.6.12 / USP (“Microbial Enumeration Test”), in Ph Eur 2.6.13 / USP (“Test for Specified Microorganisms”) and Ph Eur 2.6.1 / USP (“Sterility Test”)test is to ensure the quality and functionality of the media before using it for analysis. GPT should be performed on solid media and broths but not for dilution solutions and rinsing fluids.
GPT is performed by inoculating the product with ≤ 100 CFU of microorganisms, defined by the pharmacopoeia.  The test can be quantitative, at which 50 – 200% of the inoculated microorganisms should be recovered after incubation of the media, or it can be qualitative where the requirement is “growth” or “no growth”. GPT is described in Ph Eur 2.6.12 / USP (“Microbial Enumeration Test”), in Ph Eur 2.6.13 / USP (“Test for Specified Microorganisms”) and Ph Eur 2.6.1 / USP (“Sterility Test”)