We are professional consultants guaranteeing global standard level service to support GXP activities in development and commercialization of medicinal drugs, regenerative medicinal products, medical device and cosmetics, etc.
It is well known that establishment of the safety and efficacy of the product candidates through clinical investigations is required under Pharmaceutical Affairs Law and its related regulations for commercialization of a pharmaceuticals, regenerative medicinal products, and/or medical device etc., and thus a planning of the strategic approach for how to establish assurance of the product quality securing the safety and efficacy, is quite important even in an early development phase, as adequateness of such strategy shall be demonstrated with scientific sound into marketing license application finally. In other words, the effective control strategy for manufacturing and quality control of the new medical product shall be established during the development stage, and confirmed through process performance qualification (PPQ) activity as the planned control strategy is necessary to assure the robustness of the manufacturing process for commercial production. Global competent authorities including Japan require the license applicant to establish and maintain an internal quality management system to ensure that the product quality is assured as planned through continuous monitoring of the control strategy during the whole life cycle of commercial medical product.
In Europe and USA, the detailed information for how to perform manufacturing and quality control will be required to disclose in a clinical trial application/dossier (Investigational New Drug (IND) application and Investigational Medical Product Dossier (IMPD)), and to follow strictly such descriptions about manufacturing and quality control for assurance of effectiveness and safety of the clinical trial materials. The competent authorities further require to establish effective quality management systems to keep updating of the dossier in a timely manner, through adequate change control procedure, and will take an on-site inspection to confirm the adequate enforcement of such management system even in the development stages.
You must bear in mind that it is a recent trend the authorities would like to check clinical material manufactures during inspection to see if the appropriate quality management systems are implemented in place based on quality risk management (QRM) engagement, while credibility and justification of data accumulated under effective quality management system, including requests by a sponsor of the clinical trial will be finally checked at pre-approved inspection (PAI), together with scientifically justified determination of the product critical quality attribute (CQA) and critical process parameter (CPP) through appropriate knowledge management system. Consequently, urgent implementation to establish the robust quality management system operated mainly by Quality Assurance (QA), is considered important.
The parameters of control strategy for manufacturing the product with targeted quality, which are necessary in the future to provide the quality assurance to the medical products on the market, shall be well constructed from early development stage by accumulating scientifically meaningful data to prove the safety and efficacy of the medical product candidates. For this reason, it is necessary to demonstrate that data has been produced under compliance with the requirements of GLP (Good Laboratory Practice), GMP (Good Manufacturing Practice), GCTP (Good Gene, Cellular, and Tissue-based Products Manufacturing Practice), GDP (Good Distribution Practice) and GCP (Good Clinical Practice),and also been handled under reliable quality system providing assurance for accuracy and completeness (data integrity). Accordingly, a special knowledge and practical expertise are required for your company to support your activities in medical product development stage. Particularly, if your product is planned to market overseas (in Europe and/or USA) you must bear in mind that there are many differences in regulatory requirements and practice between these countries and Japan and thus it will be a key message to work together with competent GxP consultants who are very familiar with such regulations and rules, and also well experienced to prosecute the new drug applications in order to receive an expedited review and approval by authorities for manufacturing and marketing license. In addition, a good advice and suggestions by talented consultants will work out to reduce the risks for product recall and/or suspension of manufacturing as a result of inspections by the authorities overseas. For example, FDA will request usually to conduct extensive investigations through quality risk assessment to check if the deficiencies discovered during inspection would affect any quality impact on all of the products exported to US market, and this investigation would usually consume huge time, heavy workload and also much money. In this regard it is well known that FDA will strongly recommend to hire qualified outside GMP consultants to implement these investigations. This means FDA will no longer rely on the current quality management system operated by the company (senior managers and/or quality assurance group) to ensure the adequateness and credibility of the result from the investigations requested. Further there was a case that FDA requested to change QA Head due to insufficiency of his competence. This suggests it is the responsibility of senor manager to establish and maintain effective quality management system to ensure that daily work is in compliance with EU and/or US regulations.
After approval of commercial marketing license, the high performance level of pharmaceutical quality management system (PQS/QMS) is required to meet several requirements under GQP (Good Quality Practice) in addition to GMP (GCTP) and GDP, and the global regulations indicate clearly that it is a responsibility of the senior managements to establish and well maintain the internal quality systems (PQS/QMS), by incorporating the suppliers, contract manufacturers, and even distributers or wholesalers. In this regard, FDA and EMA will check the effectiveness of your PQS/QMS through their inspection and if any of major GMP deficiencies are found, planning and enforcement of effective CAPA including renewal of quality management system will be ordered to the senior managements due to a luck of their positive participation though it is their duty. In Europe, Qualified Person is required under EU regulation to certify that the products imported outside EU were manufactured at the facility under GMP equivalent to EU GMP, and met the pre-defined specification before released into Europe. QP is obligated to check equivalency of GMP at the facility through periodical on-site audit. Thus, clinical sponsor and/or marketing license holder shall keep a close cooperation with Qualified Person and the manufacturer by a robust quality management system, as is critical to assure product quality for clinical and/or commercial supply in Europe. It is noteworthy that some authorities have ruled out that the sponsor or license holder shall report to the authorities about insufficiency of the GMP compliance status of the manufacturing site, if they are observed.
NOBBIO Consulting is one of the qualified consulting firms in Japan with high level of specialties and expertise in GXP field, which has been demonstrated through many successful achievements of compliance supporting activities for inspection by authorities, including mock audit and professional advice for inspection readiness, based on abundant experiences on consultation for inspection by authorities. Further NOBBIO Consulting can provide consultation at every stage of product development and also commercialization, preparation of clinical trial application and marketing license application, including technical support for scientific proof relating to “critical pass” of each development stage and for negotiation with competent authorities for approval of New Drug Application (NDA)/Biologics License Application (BLA) in a timely manner.
Besides above, we have established a global business network with qualified overseas GXP consulting firms that retain the talented experts with experience of a director or senior manager of Quality (Assurance) function at big global pharmaceutical companies, bearing the responsibility to manage and establish the effective quality assurance systems for the investigational medicinal products and/or commercial drug products. You therefore will be able to receive the excellent services for compliance with global GXP regulations for medical supplies, and technical advice about necessary data required under GXP regulations in accordance with development stage, i.e., from pre-clinical stage and/or clinical development stage until commercial manufacturing after approval of a marketing license. Consultation service is also available to help you in arrangement of the meeting with authorities for discussion and agreement to proposed product development strategy and regulatory issues toward final approval of marketing license, including documentation issues (CTD filing) and any of quality issues encountered during the development stage. If you are concerned about security and completeness of your supply chain, we will be excellent to help you to provide compliance supporting activities including but not limited to audit and surveillance/supervision of the suppliers and contract manufactures around the world, in light of readiness for inspection by global authorities, like FDA and EMA etc.
The competent features of NOBBIO Consulting LLC
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- High specialties in GXP compliance practice and license application prosecution with enriched knowledge of EU, USA and Japan regulations
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- Abundant experiences about GXP compliance audit to overseas manufacturer and testing facilities
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- Guaranteed for sustainability of GXP compliance
- 1.High specialties in GXP compliance practice and license application prosecution with enriched knowledge of EU, USA and Japan regulations
- NOBBIO Consulting assures their staff has many specialties in GXP field with abundant experiences, inter alia, professional evaluation of GXP compliance status quo at manufacturing and/or testing sites in the world, and expert advice of deficiencies to be checked during inspections by domestic and overseas authorities. In addition, we have constructed a global business network with qualified overseas GXP consulting firms that retain the talented experts with experience of a director or senior manager of Quality (Assurance) function at big global pharmaceutical companies, so that we are enjoying a good reputation as highly specialized consultants in many quality issues, such as process validation and cleaning validation, deviation handling and CAPA management, Quality by Design (QbD) and changes after approval of the license (compliance to Q12), data integrity and computer system validation, quality risk management (including establishment of contamination control strategy (CCS)), as well as GDP issues such as falsification prevention measurements and documentation management of distribution records. We are also enjoying a reputation of talented expert in many regulatory issues during development period relating to planning of control strategy and validation strategy to comply with requirement under ICH Q8 and Q11.
You will therefore be entrusted to receive reliable advice and supports for updated GXP compliance requirements, and recent regulatory practices for documentation review by FDA and/or EMA. As a matter of fact, we have received many requests by US and EU companies to audit Japanese manufacturing companies/sites to check out their compliance status to US or EU GMP, and vice versa (audit request to USA and EU companies by Japanese companies).
Further, we will provide expert advice for strategic approach to promoting preparation and filing of CTD documentation, taking into consideration of product characteristic and development stages, including benchmarking and/or road mapping as development stage proceeds, assurance of data quality by performing analytical method validation/verification at early development stage, and estimation of permissible residues or exposure limit from toxicological data in pre-clinical and clinical trials for the purpose of accumulation of validated data for cleaning procedure, since these strategic arrangement will be useful to assure compilation of the necessary data into the application dossier and sometimes very helpful to shorten review process by the authorities for license approval.
Of course, we will provide best support in a timely manner to any questions about regulatory issues in the CMC field of CTD (CMC area), through competent domestic or overseas consultants in our network, if necessary.
These consultations with high specialties in regulatory prosecution and GXP compliance will not be available to you without enriched experiences in cope with regulatory inspections and negotiation with reviewing authorities. You will thus be proud of our absolute technical and business advantages which cannot be provided by other companies like engineering firms, equipment and device suppliers or consulting firms in Japan that retain consultants with carrier at domestic pharmaceutical companies.
- 2.Abundant experiences about GXP compliance audit to overseas manufacturer and testing facilities
- NOBBIO Consulting retains a specialist with abundant experiences in managing and controlling overseas manufacturers and testing organizations, or raw material venders/suppliers in Taiwan, China, South Korea, Singapore, and India, as well as USA and Europe, particularly in the field of aseptic products, bioproducts and regenerative medicinal products. In those fields, the auditors must be qualified to have specific technical and scientific knowledge about regulatory requirements for the facilities and equipment (hardware field), and also evaluation skills for adequateness of the corresponding SOPs and training/qualification records of operators (software field), so that the auditors who participate in an audit oversea could perform high quality of compliance check based on his/her knowledge and specialty about GXP regulation and technologies. In addition, you must bear in mind that the auditor must has a good language skill (at least English) to keep high quality of audit via close communications with auditees.
In addition, the manufacturer and suppliers of raw materials are not obligated to be in full compliance with GMP regulations, and thus it is well recognized that good strategy for how to manage and control these companies, particularly if they are aboard, is very important for the purpose of supplier management and by what standards shall be applied. Therefore, it is recommendable that you need knowledge about what compliance level the global big pharmaceutical companies request the suppliers to follow, and negotiation skill to persuade them to compromise with complicated business arrangements. We are well experienced about these negotiations and will be able to reach to the conclusion with the manufacturer or suppliers to the same level of manufacturing and testing control as requested by the global pharmaceutical companies.
Our overseas business partners also have abundant experiences of audits in chemical API and formulations (solid or liquid) field, and raw material supplier as well, so that you will be capable to effectively manage such companies on a daily basis or even periodically through our oversight services or by our overseas business partners and supervise them if there is something to change or deviate from the procedures and specifications.
You must bear in mind that the contractors and suppliers management is one of the major GXP issues and will be checked for adequateness when inspected by the competent authorities. Accordingly, you, as a sponsor for clinical trials, marketing license holder or contract giver will have to bear heavy burden to confirm the compliance status of contractors and supplier by periodical check of their product quality and monitoring/maintenance status of facility/equipment and process, which in turn requests that your auditors must be qualified to have enough knowledge of global regulations and standards (IPAC GMP, APIC GMP etc.,) in addition to high level of auditing skills to find quickly any deficiencies with precise evaluations. Otherwise, you will be faced with the situations that the number of quality issues relating to the products manufactured with the materials provided from such suppliers is increasing or many critical/major deviations are reported. This is because your auditors have overlooked critical deficiencies or misunderstood that CAPA has been implemented effectively for complete resolution of root cause of deficiencies and/or deviations reported. Consequently, as a result of authority inspection in the future, you will be ordered that your products shall be subject for suspension of manufacturing or product recall (mandatory or voluntary) due to lack of sufficient assurance of product quality or critical failure of your quality management system. It is very common under such situation that you will be also ordered to conduct carefully huge scope of investigation to evaluate if any lot of your products already released to the market would be also affected to its quality by the deficiencies discovered. If this is a case you cannot continue sales of suspected products and production using the materials concerned until the investigations close with successful result. Further the deficiencies may lead to render suspension of review or withdrawal of your pending license applications such as NDA or BLA, or at worst case scenario cancelation of approved license of other products on the market. It is obvious that this situation would provide critical damage to your business.
NOBBIO Consulting is highly trained to find weak points of GXP compliance, particularly vulnerability of quality management systems at the same level as the inspectors of competent authorities observe, and to explain how to manage the CAPA implementation necessary to be improved adequately and effectively. Accordingly, it is obvious that our professional support through due diligence inspections and/or periodical audits would contribute to strengthen your quality assurance system for monitoring and supervising the third-party facilities, because we can provide an audit report (English) explaining in detail all of the observed GAPs against global GMP regulations, so that you can share with the auditee the nature of the deficiencies and therefore move to the appropriate changes and/or improvements (i.e. CAPA) quickly. It is worth to know that we can take an audit in English without help by a translator. Further, our specialties can help your contractual activities with outsourcing companies for drafting and prosecuting through many revisions manufacturing and/or testing agreement, supply agreement and also quality agreement, so that you can maintain good business conditions and understand clearly mutual responsibility necessary for effective supplier control. Our service is expanded for registration and maintenance of (Drug) Master File, foreign manufacture accreditation under Japanese regulation and prosecuted as a domestic agent or representative of your company. It shall be noted that we believe our services for suppliers and contract acceptors would definitely contribute to your readiness for authority inspection, so that you can manage effectively to control these suppliers and contractors under low risks and low cost, even in an early stage of your project.
- 3.Guaranteed for sustainability of GXP compliance
- NOBBIO Consulting has established a business system to collect, by ourselves or through cooperative overseas consulting firms, the latest inspection trends by FDA (Warning Letter) and EMA (Non-compliance Report), and prospective changes to GXP regulation and corresponding guidance together with information about possible influence to current practices by global authorities, so that you can strengthen and reinforce the sustainable (pharmaceutical) quality management system ensuring compliance to the latest regulatory requirements over a product life cycle through our consulting service.
Interestingly, the scope of our support and advice can be extended to a long-term project such as new product development and/or renewal of GXP compliance management systems to domestic and overseas facilities in the field of aseptic products, bio-products and regenerative medical products, but also short-term consulting in the specific issues, such as data integrity, process validation, PQS and/or Quality Culture establishment, as well as in-house seminar about a specific subject matter. These activities will help you to significantly increase your employees’ understanding of compliance requirements for global GXP, including your managements to realize their responsibility and obligation under GXP regulation, as well. Consequently, our service could finally be resulted to establishment of sustainable your internal quality assurance system.
Further, if you have received the notice for inspection by domestic or overseas authority and it will be taken shortly, we will arrange for mock inspection and provide you quickly with our expert advice about possible corrective actions and/or necessary data to compromise any critical/major deficiencies observed, including qualification and maintenance of the facilities and equipment, risk analysis and proper evaluation, documentation of deviation/OOS and change control, etc. If you have a time to the inspection scheduled, we will evaluate your risk management system to supplement and adjust sufficiency to risk assessment for root cause investigations in deviation and/or OOS cases, change management, and CAPA management including effectiveness check, and also adequateness of control procedures and documentation for such activities, including SOP compliance, verification/validation, data integrity, training/qualification of personnels etc., so that the possibility for successful inspections by the aithority will be increased.
We also offer to help you how to manage the inspection, including preparation of the explanation materials and copies of your GXP SOPs, training of behavior by the personnel concerned, and how to respond to the questions by inspectors when interviewed, and what information or data shall be provided to the inspectors upon request, etc. If inspection readiness seems to be uncompleted within a scheduled time period, due to lack of reasonable man power resources, we will prioritize the issues based on a result of risk analysis and focus on the area identified as critical or major, which would be helpful to prevent issuance of warning letter or non-compliance report, at least, so that you could keep sustainability of your business without any concerns for suspension and /or recall of your product.