Issue link: https://www.e-digitaleditions.com/i/1118782
Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 19 analysis or online leak testing are creating some excitement, according to Eon. The implementa- tion of such online test methods might be ex- tremely challenging and costly, though, accord- ing to Schoenknecht. He points to an alternative approach that in- volves precise process validation of the filling process using the helium leakage method to en- sure selected process parameters correlated to robust process performance. After much discus- sion within the industry, there seems to be con- sensus that the helium leak test method is one of the best methods for CCI. Lonza has developed proprietar y CCI technolog y based on helium leakage testing in which prefilled syringes can be assessed in a very sensitive way, according to Schoenknecht. Helium gas leakage from samples is detected by mass spectrometry, with the ion counts proportional to the leak rate and thus quantifiable. The test can be used for vials, sy- ringes, and other drug product formats at a range of temperatures, including with Lonza's method down to -80 °C. Automated inspection for prefilled syringes Automatic inspection equipment is used to check the product for particles, for cosmetic defects, and for proper placement of the plunger, says Sacha. With automatic inspection, Eon notes, companies can enact 100% inspection instead of statistical process control, which is limited by the sample error. "Using 100% inspection ensures the lowest customer risk, enables parts per million quality level, and acts as a tool for process optimization and capability analysis," he asserts. Schoenknecht agrees that automatic control can ensure a 100% inspection of all syringes/ containers per production batch following a ro- bust reliable and reproducible testing process. "As such, a higher quality standard than for visual- only inspected syringes can be reached by calcu- lating performance data out of the data pool of syringes coming out of the glass converting pro- cess and following handling steps at the syringe vender, helping to understand the robustness of the production process applied at the place of sy- ringe production. However, inline CCI testing of the filled container usually has quite low sensi- tivity, and thus it is arguable if product quality is improved by using current CCI technologies on-line," he observes. It is important to note, though, that visual in- spection of prefilled syringes is required under GMP. In addition, automated inspection instru- ments/methods need to be qualified/validated and the automated inspection system should per- form as well as a human operator regarding fail- ure detection rates, according to Schoenknecht. False-positive detection and creating too many false rejects can occur, and users of automatic in- spection systems should be aware of the poten- tial for such issues. He also notes that for smaller batches, such as for clinical studies, manual in- spection is often preferred. References 1. Code of Federal Regulations, Title 21, Food and Drugs (Government Printing Office, Washington, DC). 2. EC Regulation 2017/745, Medical Devices (Brussels, 5 April 2017). 3. European Commission, EudraLex, Volume 4, EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use, Annex 1, Manufacture of Sterile Medicinal Products (EC, December 2017). 4. FDA, Guidance for Indu str y and FDA Staf f: Cur rent Good Manufacturing Practice Requirements for Combination Products, (CDER, January 2015). 5. PDA, Prefilled Syringe User Requirements for Biotechnology Ap- plications, Technical Report No. 73 (2015). PT