Bob Tribe_EN

nullPreparing for Regulatory GMP InspectionsPreparing for Regulatory GMP InspectionsBob Tribe Canberra, AustralianullPreparing for Regulatory GMP InspectionsOverview Secrets of success Actions before, during & after the inspection Inspection do’s and don’t’s Responding to the inspection report nullSecrets for SuccessBe well prepared. First impressions are important. Careful selection of people who front the inspectors, ie. technical ability, confidence, presentation, etc. You should convince the inspector(s) that: everything is under control. that you know what you are doing. Different perspective (seek independent advice). nullSecrets for SuccessHave a documented procedure to define: How to manage an inspection (from start to finish). inspection behaviour by staff (honesty, co-operation). The procedure for an “unannounced” inspection. Roles and responsibilities (security, reception, escort, inspection coordinator, scribe(s), subject matter experts, runners, etc.). Company policy on: entering controlled areas. Taking photos / video evidence. Taking copies of electronic data. taking samples of raw materials / products.nullRemember the Rule of the 4 BP’sBe Positive Be Polite Be Pleasant Be ProfessionalnullBefore the InspectionEstablish when the inspection is likely: If an initial or pre-approval inspection: ask regulatory authority. If a routine re-inspection: anticipate when. Determine the scope of inspection: Ask for an inspection plan. Do some research: Previous inspection reports (own files; other companies). Intelligence on the inspectors (network to find out from others; areas of expertise & focus; request their CVs). Google the inspector(s); Check for their profile on “Linkedin”. Web site information (GMP Guides & Guidelines; Q & As, inspection procedures, policies, complaint’s procedure, appeal rights, etc).nullBefore the Inspection Prepare or update Site Master File (SMF) and forward to regulatory authority. As this is usually 1st document to be reviewed by the inspector, set good first impression by: Following requirements of PIC/S PE 008-4 (SMF Guidelines). Treat SMF as a controlled document (doc. #, pagination, etc). Have SMF independently checked for grammar & spelling. Review documentation: Know the location of relevant documentation for easy retrieval. Ensure only “controlled copies” are in use. Review current documented procedures against actual methods used.nullBefore the InspectionDefine likely “tour routes” through the facility. Select a host for each location. Prepare mock questions for each location. Do a mock inspection to prepare people in each location. Undertake comprehensive internal inspection against the relevant GMP requirements: For initial inspections: use of a GMP consultant can be useful. Use PIC/S Aide Memoires where possible. Identify weaknesses & deficiencies and correct them. Use risk-based approach to grading deficiencies. Focus on the “most common GMP deficiencies” reported by regulatory authorities (eg. available on EMEA, MHRA & FDA web sites).nullBefore the InspectionEnsure the “tour” routes” are clean & presentable. Remove any obsolete or unnecessary procedures. Remove any obsolete equipment: label & store appropriately. Remove any extraneous or unnecessary postings. Empty rubbish (trash) containers. (some inspectors will examine rubbish/scrap). Clean all work areas. Ensure exterior surrounds of building are clear and tidy. (some inspectors will look for defective equipment, empty raw material containers bearing old QC status labels, etc.). nullBefore the InspectionFor newly introduced or revised SOPs/documents: Provide training to relevant personnel on these SOPs/documents Ensure that there is documentary evidence of this training. If GMP consultants are used at any stage: Obtain CV of each consultant used. Have evidence that the education, training and experience of consultants used was formally assessed. Maintain record of name, address, qualifications & type of service provided by each consultant. Particularly important for API manufacturers (clause 3.3 of Q7A GMP Guide).nullBefore the InspectionBrief & train staff on how to conduct themselves, eg: Be polite & helpful, but do not provide or say more than is required. Give “Yes” or “No” answers where possible. Do not try and second guess the next request. Do not be obstructive or argumentative. Be aware of “the silent treatment” & avoid the temptation to say something. Brief & train staff on the different inspection techniques usually used by regulatory inspectors: Helps staff anticipate the next step in the inspection process. Therefore, staff can be more proactive and get prepared for the inspector’s arrival at the next stage.nullDifferent Inspection TechniquesTrace forward: Most common approach. Start with a raw material & follow production flow. Trace backwards: Review history of a specific batch of product. eg. final product processes raw materials. Usually used to investigate cause of product defect leading to complaints and/or recall. Random: Start from points that appear significant. eg. PQR Complaint CAPA Change Control Training. Often used for pre-approval inspections. nullBefore the InspectionFor pre-approval inspections, anticipate the areas of focus and ensure all relevant documents are in order, eg. For qualification, pivotal or bio-batches: Change control, deviations & trend evaluation. Process validation reviewed against batch records. Laboratory systems: Sampling & testing of starting materials & products. Stability testing program. Supplier approval program. Contamination control for facilities & equipment. Quality System review: Batch release, discrepancy management, investigation completeness, complaint handling.nullBefore the InspectionAnticipate and keep abreast of changes to GMP requirements by visiting relevant regulatory web sites. Commence early implementation of any new GMP requirements, even during the transition period (when there is usually no legal obligation to comply with the new requirement). GMP inspectors will be impressed to see that you have commenced early implementation of expected changes to the relevant GMP requirements.nullBefore the InspectionDecide about translation arrangements: Select several staff members with good English, or Use a professional translation service (at least two translators, preferably with technical background). Simultaneous translation works best: Can be expensive, but company staff benefit by being free to devote their attention to the inspectors. Request translators with some technical knowledge. The use microphones & ear pieces. Brief translators on the day before the inspection. Make the necessary arrangements. nullBefore the InspectionTransportation of inspectors to the facility: Offer to drive inspectors to and from the facility. Driver should phone ahead to enable senior staff to be at front entrance to greet the inspectors. Display a sign or computer screen greeting the inspectors by name. Have meeting room available for the inspectors. Include country flags, flowers, tea & coffee facilities, etc. Have several scribes designated: As the inspection team likely to split up at some stage.nullArrival & Opening MeetingFriendly greeting from Inspection coordinator. On arrival, could check identification of the inspectors. On arrival, ensure they register in visitor’s book & are given name badges. Reconfirm scope of inspection. Request inspection plan (in order to have key staff available). Have your own “war room”. If not offered, request summary session at the end of each day.nullThe “War Room” (or Operations Room) Supports the people fronting the inspectors. Needs senior people in charge to support staff. Coordinates: Keeping track of the inspectors’ location. Keeping the schedule on time. Temporary staging area for documents likely to be requested. Reviewing documentation before submission. Lining up & preparing the subject matter experts. Passes on information to Senior Management on progress, areas of attention & any significant deficiencies noted. Be aware that some inspectors will seek out & visit the war room.nullOpening Meeting Advise inspector(s): Company health, hygiene & safety rules. Company policy on photographs, video & sound recording. An escort will be provided at all times while at the company. If a question cannot be answered by the escort, the responsible person in the company will be found to provide the answer. Normal operating hours are (eg. 8am to 5pm). Set the times for breaks, at lunch, coffee, end of day. Offer lunch on site. Keep company’s opening summary succinct. nullOpening Meeting Two short presentations by company suggested: 1st presentation giving brief background on company, eg. brief history, product range, site & factory layout, staff structure, etc. Do not cover sales/marketing issues. 2nd presentation giving company safety rules, including: Safety rules & warning signs; no smoking; closed shoes to be worn (no high heels); rules regarding jewellery, watches, etc. Visitors (including inspectors) will be escorted at all times. Personnel protective garments to be used as instructed. In case of emergency (fire, earthquake, etc) What alarms will sound Evacuation procedure & assembly area(s)nullDuring the Inspection Mark photocopies given to inspectors as “uncontrolled copy” &/or “commercial-in-confidence” (as necessary). Keep copies of everything given to inspectors (or at least a list of documents given): Make sure current version is given. Attempt to correct deficiencies immediately: Provide evidence while inspectors still on site. This may impress the inspection team. Request that such corrective actions be acknowledged in the final inspection report.nullInspection Do’s Do act in a courteous & professional manner. Do escort the inspectors at all times. Do answer inspectors’ questions honestly & directly. Do provide documents in an accurate and timely manner. Do ensure consultants take a low profile. Do allow inspectors to question any staff member. Do attempt to clarify or correct misunderstandings or assumptions. Do try & encourage inspectors to discuss their observations at the actual time they are observed. Do prepare internal summary of the inspection each day.nullInspection Don’tsDo not try and hide information. Do not volunteer any more information/documentation than has been requested. Do not argue or display anger, even if you are frustrated. Do not steer inspectors away from a staff they want to talk with. Do not guess the answer; tell the inspectors you will find the responsible person. Do not cause deliberate delay. Do not ask if you can help an inspector who is looking around without asking questions. Do not leave inspectors alone while in your plant. nullThe Closing Meeting Scribe should attend to compare deficiencies presented with what he/she recorded. Question deficiencies that you do not understand; seek clarification. If a deficiency is clearly wrong, suggest the inspector re-visit the area or document. Discuss any deficiencies that are clearly outside the scope of the GMP Guide.nullThe Closing Meeting Be cooperative & commit to providing a written response with objective evidence of corrective actions within an agreed time frame. Do not be argumentative. Indicate who will be the company’s contact for: Receiving the inspection report. Answering any queries inspectors may have after leaving the site.nullAfter the Inspection One person should coordinate corrective actions and written response to the regulatory authority. Use internal CAPA system to correct and close out each deficiency. Provide “objective evidence” with the response. Respond by the deadline set by the regulator. Conduct post-inspection review of areas of weakness, & take corrective action (particularly through staff training): Weaknesses identified by regulatory authority. Weaknesses identified by escort & not detected by regulatory authority. nullSecrets for SuccessBe well prepared. First impressions are important. Careful selection of people who front the inspectors, ie. technical ability, confidence, presentation, etc. You should convince the inspector(s) that: everything is under control. that you know what you are doing. Different perspective (seek independent advice). Have an SOP on how to handle regulatory inspections.