21 CFR Part 211

21 CFR Part 211 Introduction.

To achieve 21 CFR Part 211 compliance there must be a comprehensively designed and correctly implemented system of compliance with cGMP rules and regulations.

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 CFR Part 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‚Äôs suppliers and by the distributors.

To achieve 21 CFR Part 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 as legislated for in 21 CFR Part 211, 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

There is a procedure in 21 CFR Part 211 for self-inspection and/or quality audit. Records must show frequent audits for compliance.

Quality Assurance; as detailed in 21 CFR Part 211, 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 CFR Part 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 21 CFR Part 211, 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 IAW 21 CFR Part 211 legislation.
  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 in 21 CFR Part 211 for self-inspection and/or quality audit, which regularly appraises the effectiveness and applicability of the quality assurance system.

21 CFR Part 211 General Requirements.

GMP relevant Documents must be approved, signed and dated by appropriate and authorized persons.

Specifications describe in detail the  21 CFR Part 211 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.

GMP relevant Documents should be approved, signed and dated by appropriate and authorized persons.

In accordance with 21 CFR Part 211 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; as per requirements in 21 CFR Part 211, 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; in accordance with 21 CFR Part 211 legislation 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 made available by 21 CFR Part 211 is readily available throughout the period of retention.

21 CFR Part 211

SOP for Spreadsheet Creation. -- $125.00

Why does something as simple as a spreadsheet figure in so many regulatory citations?  Good question; 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; as is the requirement in 21 CFR Part 211. 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 by the user, their supervisor and QA, it becomes acceptable data stored in hard-copy, and Part 11 does not apply.


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

This matrix gives a clear and concise overview of all spreadsheets in company use.  It indicates the current validation documentation status and the individual spreadsheet issue levels.  This matrix is a regulatory required document; as per 21 CFR Part 211.


Vendor Audit Document (Issue 5) -- $105.00

This Computer Vendor Audit document should be customized using the find and replace word feature.  The document can then be re-focused to reflect your project priorities.  The fifteen chapters all contain 10 questions applicable to 21 CFR Part 211.  The total scored is then weighted to reflect your priorities.  By assessing the importance of each of the chapter subjects in your project, the weighting is altered taking points from one and adding to others.  For example in a recent audit, after weighting, order of priorities became; delivery number one, validation number two, and price trailing at number nine.  The document has been used to audit major computer equipment suppliers including two of the major DCS system suppliers in the petro/pharma/bio world.   
Use it wisely it is a very searching audit tool, and completely removes the possibility of suggestions that personal biases and opinions influenced the final audit decision.  When you audit with this document; they know they have been audited for compliance with 21 CFR Part 211, and you have the documented information to advise your company or client on the suitability of the vendor.</div>


Performance Qualification (P1Q) (Issue 5.) -- $89.00

The Performance Qualification is the last of the qualifying tests that equipment and processes are subjected to, prior to the actual first product run.  It maybe that there are some steps in the process that can only be verified by actually running them (quick freezing and sublimation, to mention only two) or it some-times is the fact that the product is a very expensive product, and can not be wasted.  So no one wants to run the process with product, until they are completely certain there will be minimal waste; 21 CFR Part 211 refers.