Applicability of Design in Pharmaceutical manufacturing industry

Applicability of Clause 7.5.2 

Exclusion of cl. 7.5.2 in case of pharmaceutical manufacturing industry is not permissible. In fact requirement of validation has been prescribed in Schedule M of Drugs and Cosmetics act and is applicable to all types of pharma manufacturing industries. Hence no pharmaceutical manufacturing (whether responsible for D&D or not) company can claim design exclusion. If the CB auditors accept such exclusions then they would not be considered competent for auditing Pharma (Scope IAF 13) sector. Further all significant changes in respect of new/changed formulation  new equipment, new process, new raw materials (including changes in suppliers of significant raw materials) / components, new test/ measurement methods as applicable), new computer systems (as applicable), new facility and or facility services, etc, would require the changes to be validated as appropriate. The organization would require documenting its system for validation to cover all necessary technical and regulatory requirements and it is expected that the CB’s auditors audit these aspects for all pharma manufacturing units.     

Applicability of Cl 7.3

As far as design & development as specified in ISO 9001, with reference to pharma sector is concerned, it is very difficult to categorically say that D & D will be applicable or not applicable, across board. This has to take into account the different types of units engaged in manufacture of pharma products as given         below:

1. First level are those organizations which are involved in R&D work for development and manufacture of new drug molecules/bulk drugs. In these cases 7.3 will definitely be applicable.

2. Second category of Pharma manufacturers are those who manufacture bulk drugs (the drug molecule which are already established). These would at the most need to establish their manufacturing process only and hence they can take the route of process validation and 7.5.2 would be applicable.

3. The 3rd category of manufacturers are those who manufacture formulations like tablets, capsules, liquid orals, etc. The design of the formulation would include as a minimum the composition (active ingredient + exepients + additives like stabilizers, Coating, colours, etc.), the Primary packaging materials and in some cases some processing aspects. Who ever is the owner of the formulation (including the packaging) would become responsible for the design of the product. It is not always necessary in pharmaceutical formulation manufacturing industry that the owner of the formula is the manufacturer.

As per the practices prevalent in the industry there are different types of arrangements for manufacturing:

a.    The owner of the formulation is the manufacturer himself. From a regulatory context the registration of the formulation would be in his name. So from ISO 9001 perspective, if such an industry is to be certified, then cl. 7.3 will be applicable. The manufacturer may argue stating that he had got the formulations registered long time ago and he has not introduced any new formulations and he does not design on a regular basis, etc. Then the CB’s audit team needs to establish the following for accepting exclusion to cl. 7.3:

i)             The formulation which was registered is complete in itself – covers complete composition (including active ingredients, exepients and additives), packaging material and shelf life declaration. This is necessary because the drug authorities some times register and licence a formulation based only on what they call “label claims”, which means based on label claims of some other popular brands/manufacturers, in which case the formulation is likely to be incomplete with respect to additives, etc, and hence the design will become applicable.

ii)            Second point to be considered is that manufacturer has not made any changes from the registered formulation as defined at sentence one of i) above.

 

b.    Another arrangement for manufacturing which is prevalent in the pharma industry is called “Loan licensing”, where owner (licensor) of the formulation (design) contracts with a party who has manufacturing facilities. It is a kind of job work arrangement, here the licensor provides the formulation (complete formulation – composition and primary packaging material, etc) and the  technical know how. He also either procures the raw material and provides it to the manufacturer or tells him the sources from where to procure the same and maintains some kind of control.  The label in these cases only indicates the brand name and the licensors name as the manufacturer. On the drug licence the name of the manufacturer (contracted) would generally appear. In this case after establishing the facts through examination of the loan licensing contract, the licensors drug licence, etc, the CB’s auditors should generally accept the design exclusion as justified. In case there are any changes to the formulation (including packaging, etc), the same would be the responsibility of the original licensor.  The CB auditors would require making enquiries about changes during every audit and verifying if these are based on licensor’s advice and inputs from him.       

c.    There is also a variant of the above manufacturing practice which is called as “Contract Manufacturing”. In this case one party who has a strong marketing base may enter in to a subcontracting arrangement with a manufacturer to manufacture under his brand name.  As per the regulatory requirements both the names of the manufacturer and the marketing agent will appear on the label. In these cases generally the owner of the formulation is the manufacturer and he also holds the drug manufacturing licence and consequently would be design responsible. Hence the treatment should be as described under a.i) &ii) above. However some times if the licensor is a big manufacturer with his own popular brand, he may prevail upon the manufacturer to use his own formulation, then perhaps based on the terms of the contract, design responsibility may shift to the licensor.

It is expected that CB’s auditor gathers and carefully examines all the information as above and then only come to the conclusion about appropriateness of design exclusion. In case he does not do necessary probing and gathering of information exercise then it would be an issue with respect to CB’s audit/certification process for pharma industry and also auditor competence issue. In case he has all the information that the client (manufacturer) is also the holder of the formula and consequently design responsible and yet accepts design exclusion, then certainly it is competence issue.

In both the cases as described at b. and c. above, if the organization being audited claims design exclusion, it would be CB’s responsibility to establish that adequate documentation regarding the owners design responsibility are available.

In all the above cases, however adherence to regulatory responsibility is solely the responsibility of the organization being audited and the CB’s audit team needs to verify actual compliance and not merely see the availability of necessary license documents.