Aseptic Processing Contamination Case Studies and the Pharmaceutical Quality System” is: The author concludes that the sterile dosage form contamination issues can emerge In the deficient design concepts and the dally operations of the pharmaceutical Industry determine safety and efficacy of drug products by analysis of 8 case studies. In this paper, the following system deficiencies are mentioned: production system, packaging and labeling system, facilities and equipment system, material system, and lab control.
What I learnt from this paper is the importance of supplier audit, rational design of alteration method and facilities design. Firstly, supplier audit is important. Although the author just mentioned it in the case study 5 “Parental-Grade Drug Substance Pertinacity, I think the supplier audit deficiency is also involved in the case study 3 “Modified 0. 2-micron Filter Design and Change Control Systems”. In the case study 3, the customers have been notified the change control of the vendor, and the vendor told them the change is minor.
I think the customers did not focus more on this change control and did not assess the Impact of the change control to their production. Therefore they continue purchasing ND using the filter of this vendor. In the case study 5, the API manufacturer had numerous quality problems, especially there is no equipment usage log for some equipment and this is an obvious deficiency. I believe that these problems have been existed for a long time. If the customers can conduct an effective audit of a vendor’s facility, they will refuse to purchase the API from this vendor, and then numerous adverse reactions did not occurred.
I found that supplier audit for some companies are formalization. The vendor does not like to be audited, so they Just provide the superficial things to the customer. The customer is being hindered and Just focus more on the price than on the quality. In my opinion, the relationship of the vendor and the customer should be a kind of mutual relationship. The supplier audit can help the vendor to Improve the quality of product and good quality can help the vendor to win the public praise and Increase sales volume.
The good quality of the vendor’s product can also help the customer to guarantee their finished product quality. Secondly, the rational design of validation method is very important. In the case study 1 “Aseptic Processing of a Sterile Active Pharmaceutical Ingredient (API)”, the recess simulation (I. E. , media fill) program was not adequately representative of the actual manufacturing process. The process simulation validation program is used to detect and diagnose an existing source of contamination.
However, some companies do not realize this usage, and the process simulation validation program designed does not reflect the actual situation of production. Not Just only for the simulation validation, other validations, like analysis methodology validation, equipment performance qualification, also exist this kind of problem, that Is, the method used to elated/qualify does not have a sufficient sensibility and representatives. Many perform the validation, but FDA mandates to perform validation, so some of engineers copy with it Just for FDA inspection, not for keeping the quality of production.
It is clear to cause the waste of manpower, material and financial resources. Good validation design cannot only help to maintain a robust quality system but also reduce the cost caused by manufacturing deviation. Thirdly, rational facility design is very important. In the case study 8 “Migration of Contamination Liberated during Facility Construction”, the firm did not adequately sees the risk posed by construction activities. Actually, the facility design is involved in all of the case study in this paper.
I feel it is very difficult to design facility and assess the risk, because it needs much knowledge and many experiences. I Joined the design of SQ Lab reconstruction in my previous company. Although I am familiar with SQ lab daily operation, I still feel it is very hard to design and assess the risk, especially for the design of the clean room. I remembered that when my company moved to the new plant from the old plant several years ago, the result of the environmental monitoring often exceeded the action level.
Many investigations were performed and unreasonable facility design was considered as the reason. We have 12 production lines and 6 of them have been reconstructed during 5 years. It is thus evident that rational facility design can help reduce the manufacturing deviation and reduce the cost of production. In conclusion, sound design and a responsive quality system can help the manufacturer to continue to reproducibly manufacture high quality sterile drugs. Before designing the validation program, clear purpose should be had, and it can improve the efficiency and effect of validation.