21 211.

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21 211 Introduction.

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. 

  1. The basic principles of quality assurance have as their goal the production of articles that are fit for their intended use. These principles may be stated as follows:
  • Quality, safety, and effectiveness must be designed and built into the product
  • Quality cannot be inspected or tested into the finished product:

Quality Assurance

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:

  1. Medicinal products are designed and developed in structured document way.
  2. Account of the requirements of Good Manufacturing Practice is made ;
  3. Production and control operations are clearly specified and Good Manufacturing Practice adopted;
  4. Managerial responsibilities are clearly specified;
  5. Arrangements are made for the manufacture, supply and verification of the status of all starting and packaging materials;
  6. All necessary controls on intermediate products, and any other in process controls and validations are carried out;
  7. The finished product is correctly processed and checked, according to the defined procedures;
  8. Medicinal products are not sold or supplied before an authorized person has certified that each production batch has been produced & iaw the requirements of the marketing authorization and any other regulations relevant to the production, control and release of medicinal products;
  9. Satisfactory arrangements exist to ensure, as far as possible, that the medicinal products are stored, distributed and subsequently handled so that quality is maintained throughout their shelf life;
  10. There is a procedure for self-inspection and/or quality audit, which regularly appraises the effectiveness and applicability of the quality assurance system.

21 211 General Requirements.

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 packaging operations. 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 the 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 contents; title, 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 process.

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 211.

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.

21 211

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Validation Documentation Matrix (Issue 6.) -- $29.00

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SOP for Spreadsheet Creation. -- $125.00

Why 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.


SOP for cGMP Review (Issue 3.) -- $89.00

The 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.


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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.


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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 achieved.
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The Corporate Quality Manual (CQM)is only available on DVD and is normally dispatched within two working days.


Definitive Validation Manual (Issue 5.) -- $1,160.00

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.


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