Issue link: https://www.e-digitaleditions.com/i/733311
Tablets & Capsules October 2016 13 Beware of recycling old equipment It's an understatement to say that the pharmaceutical industry is conservative: Some facilities still use equip- ment and processes from the 1970s and 1980s. In fact, it's not unusual. The industry abounds with painted-frame tablet presses that require operators to turn hand wheels to adjust performance. At some facilities, nothing has changed since the process was conceived and the equip- ment installed. Perhaps that's OK if the process works, but when new equipment eventually replaces the old, beware of repurposing the old machines in-house. I've seen equipment that should have been sold or scrapped but was instead transferred to the product development section. That seems like an economical and sound decision, but it often isn't. After all, your colleagues would inherit a machine that has no equivalent elsewhere and/or uses a dif- ferent principle of operation than the modern production equipment. Examples include planetary mixers and old tablet presses with worn turrets. I understand it may be dif- ficult for the R&D people to refuse no-cost equipment, but that's what they should do in most cases. In fact, it's coun- terproductive to accept the outdated equipment because its performance will never be representative of the process at a larger scale. In addition, because of wear and tear, old machines will likely generate unreliable data. Installing donated equipment at another production facility isn't usually a good idea either. It can take a long time to fit the outdated equipment in with more recent equipment and connect it to process controls. Consider Manesty's DryCota tablet press, which was used to develop many tablet-in-tablet products during the 1970s, 80s, and 90s (photo). Those products were eventually transferred to a facility equipped with 21st- century tablet presses like IMA's S-250 and Kikusui's Libra 2 DC. The switch to modern machinery, though chal- lenging, enables operators to confirm online that the cores are present, which the original equipment didn't. I can't stress enough the importance of making time to monitor—in depth—the donor sites to understand how the equipment there is installed, how it operates, and how it fits in the process. Ideally, come with an experienced operator from the receiving site and take photos or videos. Survey different operators to find out how they have tried to change the process, how different setups/adjustments affect results, and what they have observed behaving dif- ferently under certain circumstances. These could include seasonal changes, changes in flow behavior, and day versus night shift. Operator seniority could also have an impact because sometimes only senior operators know how to run hard-to-handle products, an ability they mastered from years of experience. The most interesting observations are those not documented in the batch record. Be sure to include them in your unofficial product history. Case study: Hiccups after upgrade Years ago, I was asked to help transfer an old product that had run on the same press for 15 years. The product was running well at an output of 1,300 to 1,500 tablets per minute (tpm), and there were no problems with flow or content uniformity during the initial process valida- tion. The product was then moved to a new facility where the press typically produced in the range of 3,500 tpm. During the trial batches at the receiving site, the product wouldn't flow at all. A long investigation and root-cause analysis revealed that at the previous site, the old, mobile press had been brought to the production area at the start of each cam- paign. It was also standard practice not to level the press, which caused it to vibrate. That helped the powder to flow. Of course, operating the press at a lower speed also helped with weight unifor- mity, but the vibrations were the main reason because the blend at both sites had the same particle size distribution. With no slower press available at the receiving site, the solution was to reformulate the blend to improve its flowability and content uniformity so it would run on the high-speed press. Validation and process understanding In some cases, the processes used to make legacy products were never validated or validated retrospec- tively based on the history of the process and product. That works well if it's done properly using, for example, statistical tools such as control cards or a process-capabil- ity index—often denoted Cpk—on relevant process para- meters and/or controls. If no validation was done, your company's specialist in technology transfer or a consul- tant will have to pull executed batch records from a rep- resentative number of lots and analyze the data. That will give you an unbiased picture of process behavior at the donor site. It will also help you design the technology- transfer plan and help you draft a comparability protocol. Other important documents Data from the site to be closed usually includes master batch records and product and raw materials specifica- tions. Within the master batch records, there is typically a section that lists the history of changes and the corre- sponding change-control numbers. With that information you can find reports and/or justification of the changes in the process, materials, and equipment. Several other documents can provide more details that will help you continue manufacturing within-spec legacy products. They include: • A certificate of analysis (CoA) for each active ingredient, excipient, and primary packaging component. The CoA will list a specific grade of material and the manufacturer's code for it, enabling you to order the exact same material. Use the most recent CoA to procure the material. One caveat: The specifications of some lots of excipients Installing donated equipment at another production facility isn't usually a good idea.