21 211 or 21 CFR Part 211 compliance requires the manager of any regulatory controlled manufacturing company to manufacture all medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorization and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this 21 211 compliance is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company’s suppliers and by the distributors.
To achieve 21 211 compliance there must be a comprehensively designed and correctly implemented system of Quality
Assurance Incorporating Good
Manufacturing Practice, and thus Quality
Control and Quality
Risk Management.It should be fully documented and its effectiveness monitored.
All parts of the Quality Assurance systems should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. There are additional legal responsibilities for the manager of the manufacturing authorization and for the authorized person(s). The basic concepts of Quality Assurance, Good Manufacturing Practice, Quality Control and Quality Risk Management are inter-related. They are described here in order to emphasis their relationships and their fundamental importance to the production and control of medicinal products.
Quality Assurance is a wide-ranging concept, which covers all matters, which individually or collectively influence the quality of a product. It is the sum and total of the organized arrangements made with the objective of ensuring that medicinal products are compliant with the requirements detailed in 21 211. Quality Assurance therefore incorporates Good Manufacturing Practice (GMP) plus other factors outside the scope of this Guide.
The system of Quality Assurance appropriate for the manufacture of medicinal products should ensure that:
Specifications describe in detail the
requirements with which the products or materials used or obtained
during manufacture have to conform. They serve as a basis for quality
evaluation. Manufacturing Formula, Processing and Packaging Instructions
state all the starting materials used and lay down all processing and
Procedures give directions for performing certain operations e.g.
cleaning, clothing, environmental control, sampling, testing, equipment
operations, as detailed in 21 CFR Part 211.
Records provide a history of each batch of product, including its
distribution, and also of all other relevant circumstances pertinent for
quality of the final product.
Documents should be designed, prepared, reviewed and
distributed with care. They should comply
with the relevant parts of the manufacturing and marketing authorization dossiers as detailed in 21 CFR Part 211.
Documents should be approved, signed and dated by appropriate and authorized persons.
Documents should have unambiguous
nature and purpose should be clearly stated. They should be laid out in
an orderly fashion and be easy to check. Reproduced documents should be
clear and legible. The reproduction of working documents from master
documents must not
allow any error to be introduced through the reproduction
Documents should be regularly reviewed
and kept up-to-date. When a document has been revised, systems should be
operated to prevent inadvertent use of superseded documents. As
detailed in Part 11 and 21 CFR Part
Documents should not be hand-written; although, where documents require the entry of data, these entries may be made in clear, legible, indelible handwriting. Sufficient space should be provided for such entries.
Any alteration made to the entry on a document should
be signed and dated; the alteration
should permit the reading of the original information. Where appropriate, the
reason for the alteration should be recorded.
The records should be made or completed at the time each action is taken
and in such a way that all significant activities concerning the manufacture of
medicinal products are traceable. They should be retained for at least one year
after the expiry date of the finished product.
Data may be recorded by electronic data processing
systems, photographic or other reliable means, but detailed procedures relating
to the system in use should be available and the accuracy of the records should
be checked. If documentation is handled by electronic data processing methods,
only authorized persons should be able to enter or modify data in the computer
and there should be a record of changes and deletions; access should be
restricted by passwords or other means and the result of entry of critical data
should be independently checked. Batch records electronically stored should be
protected by back-up transfer on magnetic tape, microfilm, paper or other means.
It is particularly important that the data are readily available throughout the
period of retention.
This Matrix must sit along-side your VMP or PVP and together with these documents give a very concise overall picture of your validation program. This four part matrix allows you to list all the equipment and systems that must be qualified. Each entry is allocated a row in the matrix. The row consists of eleven headings, these may be edited as required (but come with all the standard documentation titles inserted). In this matrix there is room to enter the document number, prefixed by, A to D. The document number gives you the instant cross reference to all the associated documents; the A to D prefix shows the progress stage.
This document follows our well-developed method of using a generic document and allowing the customer to apply an attached detailed SOP to it, turning the generic document quickly into a first class company bespoke document. This VP details and integrates all validation activities and procedures required for a small to medium sized project, involving production/facility/utility equipment using electronic controls or monitoring.
This Standard Operating Procedure (SOP) takes you through the validation process for equipment, from the very early first stages to the final closing stage. It will ensure that your validation is seamless, that the correct documents are raised, approved, executed, reviewed and accepted correctly. It shows how to use validation tools such as the very important matrix control document and equally important risk assessments. There are ever-increasing demands on the Biotechnology and Pharmaceutical industries to meet increasing regulatory and legislative requirements, whilst improving the performance and efficiency of the business. This SOP shows the way to streamline your validation while still being fully compliant. Easing and smoothing the production and flow of protocols, so decreasing costs and delivering validation ahead of schedule. It is essential material for the new comer to validation and will direct you flawlessly through all validation tasks. For the company it is an essential SOP to add to the library. For your convenience it is written in word.
does something as simple as a spreadsheet figure in so many regulatory
citations? Good question; and at times a difficult one to answer. When you ask a
group of compliance personnel the same question you will be informed that Excel
cannot be validated because it does not seal the original copy (of the
spreadsheet), allows the original to be modified and has an audit trail that can
be disabled. All true, but none of these problems interfere with your ability to
validate that the spreadsheet is fit for purpose. They only preclude you from
using the spread sheet as a compliant repository for any data that has to be
store in compliance with 21 CFR Part 11.
If the spreadsheet is signed off and dated by the user, their supervisor and QA, it becomes regulatory acceptable data stored in hardcopy, and Part 11 does not apply.
After numerous request for this, we have launched our brand new SOP for Spreadsheet Creation to cover these and other known target points that the regulators consistently hone into as soon as they find that spreadsheets are being used. Use this Spreadsheet Creation SOP to ensure that you create spreadsheets that are validatable. Then use our spreadsheet validation pack to validate them.
cGMP Review is undertaken to ensure that a design and/or facility conforms to
the cGMP requirements and is fit for purpose. The requirement for Regulatory
Compliance will be established during the proposal preparation.
cGMP Reviews should normally take place in accordance with the project programme. The initial cGMP Review should take place immediately after the project initiation, to define the cGMP Envelope and clarify the cGMP requirements. Additional cGMP reviews should be held towards the end of the front end design and detailed design.
It is good housekeeping practice for department heads to instigate periodic cGMP walk rounds to analyse, document and ascertain if every-day wear and tear to the fabric of the facility, is compromising the validated status of the facility.
The ever sought after SOP for writing an SOP. Adopting a standard format throughout a company for the easy authoring of SOP's is of immense benefit to everyone that has to use them. Our format follows our standard company developed format of a generic template prefixed by an SOP. Follow the SOP and you quickly and simply produce a sound compliant SOP document. In this case the generic SOP template is prefixed by a SOP.
The purpose of producing this document in such a concise manner, is to give a desk top reference document that can be used by authors, engineers and quality staff. It can be used in meetings, during general conversation and during telephone conversations. You first check the CPR to see what rules apply, then check out the rules in depth. You can always be sure that your documents are referenced to the correct GMP requirement.
This test script has been designed to verify whether a system or a specific piece of equipment conforms with the requirements detailed in Part11. This Test Script is not in the standard Operational Qualification (OQ), and is only available here as a direct download.
The FDA has raised the bar. The rationale for
change, the approach it has taken and the progress achieved are not as good as
some think. In September 2003, The Wall Street Journal published an article
informing all that pharmaceutical “manufacturing techniques lag behind those of
potato-chip and laundry-soap makers.” The same article correlated the rise in
recalls with quality problems and noted that despite fines in excess of US$500
million for manufacturing failures, acceptable levels of quality were not being
Since then, the FDA, and the industry have been actively, working together to shape the new quality requirements and standards. Compliance now requires a quality systems approach starting with “quality by design” in development and ending with scientific process control in manufacturing. So today, products are more complex; cash is scarcer; and quality requirements require more fundamental understanding. Pharmaceutical companies need to take action on each of these issues in a comprehensive manner.
The Corporate Quality Manual (CQM)is only available on DVD and is normally dispatched within two working days.
This definitive 1000 + page Definitive Validation Manual arrives with you in DVD format, this enables you at any time to download protocol or test-scrip documents and quickly edit them into company bespoke documents. In fact there are over $3,500.00 worth of superb documents that form attachments to the DVM manual, which can be instantly copied. Once copied, the unique document interactive editing, allows you to produce high quality bespoke company documents (weeks of work in a few hours). The cost of the Definitive Validation Manual, will be recouped in the first few weeks of use. It will then go on to show a massive return on your original investment.