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36 BioPharm International eBook July 2021 www.biopharminternational.com involved deficiencies in cleaning and sanitization and their validation. This fact was presented by Matt Cokely, senior global technical consul- tant manager for Ecolab Life Sciences in a best-practices webinar presented by t he I nter nat iona l S oc iet y for Pharmaceutical Engineering (ISPE) on April 9, 2021 (2). The most often cited problems, he said, were the lack of pro- cedures for preventing contamination, deficiencies in cleaning, failure to keep cleaning records, and inadequate stan- dard operating procedures (SOPs). Clea n i ng v a l id at ion consu lta nt R ic h For s y t h a g r e e s . " P r o bl e m s often boil down to a failure to follow cleaning procedures. Either people are doing something that is not in the SOP or there's something in the SOP that they aren't doing," he says. For example, Forsy th notes, many procedures fail to specif y cleaning frequency, or the amount of time that should be spent to clean a piece of equipment using documented pro- cedures and materia ls. This forces op erator s to ta k e t he u nprov able position that 'it's not clean until it's clean', he says. ACTIVE TRAINING NEEDED Clea n ing a nd c lea n ing va l idat ion practices need to be reproducible, Cokely noted, and employees must be trained, not only in the basics of microbiology and hygiene pertaining to cleaning, but in cleanroom pro- cedures and gowning and in under- standing potential risks and safet y hazards. "They need to understand not just how, but why they are per- forming a task, and to be trained to actually perform it," he said, rather t han simply being g iven a pi le of SOPs to read and sign off on. Given the trend to outsource cleaning and sanitization activities, Cokely noted, this training must be given to con- tract cleaning workers as well. Elaborating further, Cokely noted that w r it ten inst r uctions in SOPs shou ld specif y who is responsible for the duties, and set a schedu le of frequency for cleaning, describe the materials and techniques to be used in detail, and the preparation and storage of c leaning materia ls. In add it ion, doc u mentat ion must include the names and signatures of staff performing the work, as well as the product batch number, cleaner expiry date, and disinfectants used. Cokely also noted that disinfectants with different modes of action should be rotated. Care must also be taken, he said, to avoid interactions between different cleaning chemistries that might inhibit microbe-killing mech- anisms and promote the buildup of cleaning solution residues. The basic problem, Cokely noted on the webcast, is that cleaning and disinfection are under valued in the pharmaceutical industry, despite their impor tance to pat ient and overa l l safet y. "At some companies, clean- ing procedures have been used for years, or the facility may have inher- ited practices that have never been reviewed or scrutinized," he said. Reg ulations for cleaning and its validation abound, supplemented by best practices circu lated by ISPE , t he Pa renter a l D r u g A s s o c i at ion ( P DA ), a n d n o w t h e A m e r i c a n Societ y for Testing and Mater ia ls (AST M), which has set standa rds for pha rmaceutica l c leaning oper- at ions a nd v a l idat ion. R isk-ba sed sta nda rds for c lea n ing va l idat ion, set in 2018 (3), began to establish a more scientif ic basis for practices at individual facilities. These standards have had a pos- it iv e i mp ac t , note s For s y t h , g et- t ing pha r maceut ica l companies to go be yond t h in k ing si mply about pro duc t s , e q u ipme nt , a nd d e te r- gents in their cleaning operations. "R isk-based standa rds forced peo- ple to for ma l iz e t heir r isk assess- m e nt s . M a n y o f t h e m b e g a n t o consider periphera l risks that they hadn't factored in before, such as the air-handling system's impact or the material and equipment traff ic in the facility," he says. However, in the end, some compa- nies may view having a formal clean- ing validation program and strategy as involving too much work. "Companies pay a lot of attention to their clean- ing and cleaning validation programs when they get cited by regulators for those programs' failings," Forsy the says. But establishing a program or updating one that hasn't been reviewed in several years, takes commitment, he notes, and it generally requires a year to do because everyone has their regu- lar jobs to do, too. "Often, shepherding a cleaning validation project through to its end becomes more problematic the longer the projects continue. At many companies the success or failure of a cleaning and cleaning validation program may rest on one champion supporting it," Forsyth says. MULTIPRODUCT FACILITY CHALLENGES Today, multiproduct facilities, and particularly biopharmaceutical facil- ities, pose severa l cleaning va lida- Biopharmaceutical Analysis Cleaning Validation The best way to remove subjectivity from inspections has been to qualify those who must perform those inspections, a step that most regulatory agencies now require.