cGMP Compliance Research Articles

Proactive Approaches to cGMP Compliance: Insights and Key Takeaways from USFDA Warning Letters to Pharmaceutical Industries Between 2019 and 2024

Proactive Approaches to cGMP Compliance: Insights and Key Takeaways from USFDA Warning Letters to Pharmaceutical Industries Between 2019 and 2024

A retrospective regulatory analysis of FDA recalls carried out by pharmaceutical companies from 2012 to 2023

To introduce products in the US market, pharmaceutical companies must first obtain FDA clearance. Manufacturers might recall a product if it poses a risk of damage or violates FDA regulations. This study investigates the types, causes and consequences of recalls, as well as FDA participation and suitable recall strategies. We relied on the FDA website to gather recall data sets from 2012 to 2023, collecting information on the date of issuance, company and type of violation. The most frequent causes for recalls were sterility issues and inadequate compliance with current good manufacturing practices (cGMP). An examination of sterility recalls revealed two primary causes: a lack of assurance in sterility (accounting for 48% of recalls) and instances of non-sterility (making up 45% of recalls). A thorough examination of cGMP recalls revealed five primary types of violations: process control issues, inadequate storage practices, manufacturing problems, the presence of nitroso-amine impurities and concerns regarding stability. The findings demonstrate that sterility and cGMP compliance are FDA priorities. Pharmaceutical companies must, therefore, enhance quality compliance and create effective quality management systems that oversee the manufacturing process, quality control, personnel training and documentation to avoid these recalls. Companies should establish an internal compliance checklist and be prepared for the rectification process.

Challenges and Considerations of Preclinical Development for iPSC-Based Myogenic Cell Therapy.

Cell therapies derived from induced pluripotent stem cells (iPSCs) offer a promising avenue in the field of regenerative medicine due to iPSCs' expandability, immune compatibility, and pluripotent potential. An increasing number of preclinical and clinical trials have been carried out, exploring the application of iPSC-based therapies for challenging diseases, such as muscular dystrophies. The unique syncytial nature of skeletal muscle allows stem/progenitor cells to integrate, forming new myonuclei and restoring the expression of genes affected by myopathies. This characteristic makes genome-editing techniques especially attractive in these therapies. With genetic modification and iPSC lineage specification methodologies, immune-compatible healthy iPSC-derived muscle cells can be manufactured to reverse the progression of muscle diseases or facilitate tissue regeneration. Despite this exciting advancement, much of the development of iPSC-based therapies for muscle diseases and tissue regeneration is limited to academic settings, with no successful clinical translation reported. The unknown differentiation process in vivo, potential tumorigenicity, and epigenetic abnormality of transplanted cells are preventing their clinical application. In this review, we give an overview on preclinical development of iPSC-derived myogenic cell transplantation therapies including processes related to iPSC-derived myogenic cells such as differentiation, scaling-up, delivery, and cGMP compliance. And we discuss the potential challenges of each step of clinical translation. Additionally, preclinical model systems for testing myogenic cells intended for clinical applications are described.

Overview of Post-approval Submissions Management in US, Europe and Canada

In today’s business era & competition in pharmaceutical industries, post-approval evaluation & cGMP compliance plays an important role. Regulatory approval is a critical milestone in the lifecycle of pharmaceuticals and medical devices, ensuring their safety, efficacy, and quality before entering the market. A regulatory affair is a bridge between pharma industry and health authorities.
 Post-Approval function in Regulatory Affairs department plays a major role in supporting continuous commercialization and facilitating for its implementation. This function are responsible to provide strategic regulatory inputs to plant team on their proposals and to facilitate smooth submission followed by acceptance/ approval. In the USA, the Food and Drug Administration (FDA) governs the regulatory process, employing a thorough and well-defined approach to submission evaluation. Europe, with the European Medicines Agency (EMA) at its helm, utilizes a centralized procedure for marketing authorization, harmonizing regulations across member states. Meanwhile, Health Canada oversees regulatory activities in Canada, emphasizing a risk-based approach to ensure public safety.
 Post-approval submission management is equally vital in maintaining compliance and ensuring ongoing product safety. This paper delves into the strategies and best practices for handling post-approval changes, variations, and renewals. It examines the role of regulatory intelligence, life cycle management, and effective communication with regulatory agencies to navigate the evolving regulatory landscape.
 By comparing and contrasting the regulatory processes in the USA, Europe and Canada, this overview aims to provide valuable insights for pharmaceutical and medical device companies seeking global market access. Understanding the intricacies of regulatory submission and post-approval submission management across these regions is essential for successful product development, commercialisation and long-term regulatory compliance.

FDA Warning Letters: A Retrospective Analysis of Letters Issued to Pharmaceutical Companies from 2010-2020.

PurposeTo launch a pharmaceutical product in the US market, approval from the FDA is required. Pharmaceutical companies undergo FDA pre-approval inspection (PAI for small molecule products) or pre-license approval (PLI for biological products) at their manufacturing sites (including contract development and manufacturing organization, testing laboratories, and packaging labelling facilities) prior to approval. After the products are approved by the FDA, surveillance inspections are performed by the FDA which are risk based as which company and which site will be inspected. The present study examines the causes of warning letters issued by the Center for Drug Evaluation and Research (CDER), FDA to the pharmaceutical companies after post-approval inspections.MethodsWarning letters issued from the time period 2010 to 2020 were obtained from the FDA website, and information about date of issuance, company, and type of violations was extracted for the study.ResultsPoor compliance to CGMP and misbranding were the most common reasons for the warning letters. Detailed analysis of CGMP warning letters elucidated three major types of violations, namely deficiencies in process validation, documentation practices (data integrity), and quality control corresponding to 26%, 21%, and 15% warning letters, respectively.ConclusionReview of the analysed letters demonstrates that the FDA’s major concern is over CGMP compliance. To avoid these warning letters, pharmaceutical manufacturers need to improve their quality compliance and focus on creating effective quality management systems that govern the entire manufacturing process, quality control, employee training, and documentation practice. Companies should develop an internal compliance check list and also be ready for corrective measures as and when required.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12247-022-09678-2.

Incubation temperature and culture medium formulation impact the accuracy of pour-plate techniques for the enumeration of industrial Bacillus assemblages

Aerobic plate counting assays based on the pour-plate technique are frequently used to enumerate microbial products; however, colony swarming and merging at the agar surface can reduce the accuracy of these assays. Some plating methods mitigate this risk through the inclusion of strategies including agar overlays; however, these interventions may be inadequate to mitigate swarming and merging of certain Bacillus colonies. In the present study, we assessed the accuracy of several pour-plate techniques for the enumeration of a mixed-species Bacillus assemblage. Tested modifications included a customized culture medium formulation, agar overlays, decreased incubation times and increased incubation temperature. Methods which produced countable plates were assessed for agreement with a Bacillus-specific plate counting assay and with total cell counts rendered by flow cytometry. While all tested pour-plate methods underestimated Bacillus endospore concentrations relative to flow cytometry and customized spread-plating, our results suggest that increasing incubation temperature and the inclusion of bile salts into culture medium formulations can improve the accuracy of pour-plate techniques when used to enumerate Bacillus assemblages by decreasing the incidence of spreading colonies. As Bacillus endospore preparations become more ubiquitous in the market, familiar enumeration methods such as the pour-plate technique may require methodological modifications to ensure that the cGMP compliance of Bacillus-based microbial products is assessed accurately.

Cell-Based Therapy Manufacturing in Stirred Suspension Bioreactor: Thoughts for cGMP Compliance.

Cell-based therapy (CBT) is attracting much attention to treat incurable diseases. In recent years, several clinical trials have been conducted using human pluripotent stem cells (hPSCs), and other potential therapeutic cells. Various private- and government-funded organizations are investing in finding permanent cures for diseases that are difficult or expensive to treat over a lifespan, such as age-related macular degeneration, Parkinson’s disease, or diabetes, etc. Clinical-grade cell manufacturing requiring current good manufacturing practices (cGMP) has therefore become an important issue to make safe and effective CBT products. Current cell production practices are adopted from conventional antibody or protein production in the pharmaceutical industry, wherein cells are used as a vector to produce the desired products. With CBT, however, the “cells are the final products” and sensitive to physico- chemical parameters and storage conditions anywhere between isolation and patient administration. In addition, the manufacturing of cellular products involves multi-stage processing, including cell isolation, genetic modification, PSC derivation, expansion, differentiation, purification, characterization, cryopreservation, etc. Posing a high risk of product contamination, these can be time- and cost- prohibitive due to maintenance of cGMP. The growing demand of CBT needs integrated manufacturing systems that can provide a more simple and cost-effective platform. Here, we discuss the current methods and limitations of CBT, based upon experience with biologics production. We review current cell manufacturing integration, automation and provide an overview of some important considerations and best cGMP practices. Finally, we propose how multi-stage cell processing can be integrated into a single bioreactor, in order to develop streamlined cGMP-compliant cell processing systems.

Abstract 3245: FT819 path to IND: First-of-kind off-the-shelf CAR19 T-cell for B cell malignancies

Abstract Genetic engineering of T cells using a chimeric antigen receptor targeting CD19 antigen (CAR19) is now a well-established treatment of B cell malignancies. While cellular immunotherapies are entering front line treatment, substantial limitations currently hamper the broad application of adoptive T cell therapies in diverse patient population including dysfunctional starting material, lack of product consistency and purity post genetic engineering and inefficient quantity produced for true on-demand availability. FT819 is a first-of-kind off-the-shelf CAR19-T cell product generated from a renewable pluripotent stem cells for large-scale clinical manufacturing. We previously reported the engineering and characterization of the FT819 clonal master cell bank (MCB) derived from a single cell comprising targeted integration of a novel CD19 1XX CAR into the T-cell receptor (TCR) α constant locus to provide optimally regulated CAR expression and elimination of graft versus host (GvH) response. Here we preview the nonclinical study for the original investigational new drug application of FT819. Derived in a manufacturing process analogous to pharmaceutical drug product development, pilot runs from the MCB demonstrated FT819 can be consistently and uniformly manufactured in cGMP compliance, cryopreserved at clinical scale to support off-the-shelf clinical application with greater than 1e5 fold increase in cellular yield from the starting MCB and can be thawed and directly used for facilitated treatment. Repeatedly, FT819 displayed a uniform product profile of ≥95% CAR+, TCR-, CD45+, CD7+ and CD3+ [intracellular] with majority of CD8 T cells expressing CD8β. FT819 global gene expression profile displayed high similarity to primary CAR19-T cells confirming its identity as a T lymphocyte. Functional assessment demonstrated that FT819 possesses potent antigen specific cytolytic activity against leukemia and lymphoma cell lines (p=0.0004). Additional specificity studies demonstrated on-target, off-tumor cytolysis of CD19+ B cells in mixed lymphocyte reaction assay (85% lysis of CD19+ B cells versus < 2% lysis of T cells). Inability of FT819 to produce a GvH response was confirmed in a co-culture assay with anti-TCR crosslinking antibodies. Disseminated leukemia xenograft mouse studies demonstrated the ability of directly thawed and infused FT819 to control tumor growth (p=0.0003 at day 21). In a systemic administered leukemia model FT819 also showed sustained localization in the bone marrow up to 45 days post injection. Ongoing in vivo studies will assess long-term survival and avoidance of GvH disease. Collectively, these studies demonstrate that FT819 is a potent, consistent and uniform CAR19 T cell product and can be effectively and safely used off-the-shelf in the treatment of B cell malignancies with an original Phase 1 clinical trial planned in 2020. Citation Format: Mili Mandal, Raedun Clarke, Sjoukje van der Stegen, Chia-Wei Chang, Yi-Shin Lai, Alec Witty, Mushtaq Husain, Cheng-Jang Wu, Bi-Huei Yang, Chad Dufaud, Gloria Hsia, Helena Shaked, Laurel Stokely, Helen Chu, Mochtar Pribadi, Gilberto Hernandez, Jason ORourke, Alma Gutierrez, Ramzey Abujarour, Tom Lee, Jolanta Stefanski, Juan Zhen, Meilan Wu, Isabelle Riviere, Michel Sadelain, Bahram Valamehr. FT819 path to IND: First-of-kind off-the-shelf CAR19 T-cell for B cell malignancies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3245.

Navigating the Maze of Dietary Supplements

Dietary supplement companies must adopt Current Good Manufacturing Practices (cGMPs) to ensure that procedures are in place in order to verify the identity, strength, purity, and composition of supplement ingredients. In addition to the Food and Drug Administration enforcement, independent regulatory agencies exist to verify cGMP compliance. Supplement companies must follow regulations governing claims, labeling, advertising, and packaging. The safety record of dietary supplements and resources to assess drug nutrient interactions are discussed. Understanding the regulatory and safety issues surrounding dietary supplements will help nutrition professionals have more confidence when recommending them as an adjunct to diet and lifestyle.

Gamma irradiated human platelet lysate as a serum substitute for ex vivo expansion of immune cells

Background & Aim Adoptive immunotherapy is emerged as one of the leading treatments in cancer. The clinical applications require ex vivo expansion of lymphocytes to therapeutic doses in a timely manner under strict cGMP compliance. Culture medium is one important determinant for successful cell expansion. Many efficient expansion strategies incorporate serum or plasma as a supplement to provide cells with a richer milieu to grow in. However, autologous serum has supply limitations for meeting the expected commercial demand for immunotherapies. Moreover, pooled human serum or animal-derived serum bring the inherent concern about risk of infection transmission. Human platelet lysate (hPL) is well recognized as an efficient xenogenic-free alternative to FBS for manufacturing cells and cellular products. To address the risk management for pathogen transmission, we have assessed the feasibility of gamma irradiation as a pathogen reduction treatment for hPL and validated its efficacy for virus inactivation. Our gamma irradiation process demonstrated low impact on hPL potency and long-term stability. In this study, we evaluated the potential use of gamma-irradiated human platelet lysate (GI hPL) on immune cell expansion. Methods, Results & Conclusion To compare the potency of different culture supplements, peripheral blood mononuclear cells were activated and expanded in the presence of interleukin 2 (IL2). T cell expansion in GI hPL supplemented medium showed higher yields than the expansion obtained with autologous plasma. For NK cell expansion, the potency of GI hPL and plasma were comparable. The cytotoxicity of NK cells against K562 cells was high and comparable for both GI hPL and plasma. High viability was observed in all expanded lymphocytes. The results suggest that GI hPL is a viable and valuable alternative cell culture supplement for ex vivo expansion of immune cells.

Determination of bioactive nonvolatile ginger constituents in dietary supplements by a rapid and economic HPLC method: Analytical method development and single-laboratory validation

Most of the validated methods for ginger-containing dietary supplements have long run time and low sensitivity and only analyze gingerols and shogaols. 6-Paradol and zingerone become popular in modern dietary supplement industry as bioactive ginger constituents. Therefore, we developed an efficient HPLC-UV/Vis method to analyze all above major constituents. Compared to 282/280 nm used by the current compendial United States Pharmacopeia (USP) monograph method and International Organization for Standardization (ISO) 13685-1997 method, detection wavelength was optimized to 230 nm which showed a higher sensitivity (signal-to-noise ratio) and better peak resolution. For measuring the ginger constituents in AOAC required matrices, the method was demonstrated to be selective, linear (R2 > 0.999), specific, accurate (91.1–103.2% spike recovery rate) and precise (RSDr < 5%, RSDR < 8%). Among 10 commercial ginger-containing samples that we screened using this method, the results were 80–123% of the products’ labeling value. The HPLC running time was successfully shortened from 29 min (USP method) and 40 min (ISO method) to 12 min without the need of using an expensive Mass Spectrometer for analyte separation. The method is the first method that meets all AOAC SMPR 2017.12 requirements and therefore has the potential to be adopted as a consensus industrial reference method for meeting FDA's cGMP Compliance for the manufacture and quality control of dietary supplements and ingredients.

PIC/S: TRAINING THE REGULATORS TO REGULATE cGMP COMPLIANCE

PIC/S is an international Organization for implementing cGMP standards in its member countries. The basic objective of PIC/S is to improve and standardize cGMP compliance in member countries. Their aim is to enhance GMP intelligence via sharing of GMP inspection reports. Further it wants to reduce duplication of inspections to save the cost and time.&#x0D; Their regulations are directed to promote harmony in GMP standards and to train national regulatory authorities for cGMP vigilance. They requires that every nation shall empower the legislation to inspect the facilities as per definite program, to issue notices for noncompliance, to impart regular training to all concerned employees.

Automated Tissue Dissociation for Rapid Extraction of Viable Cells

Viable cells from healthy tissues are a rich resource in high demand for many next-generation therapeutics and regenerative medicine applications. Cell extraction from the dense connective matrix of most tissues is a labor-intensive task and high variability makes cGMP compliance difficult. To reduce costs and ensure greater reproducibility, automated tissue dissociators compatible with robotic liquid handling systems are required. Here we demonstrate the utility of our automated tissue dissociator that is compatible with standard microtiter well plates for high-throughput processing. We show that viable cell yields match or exceed manual methods while reducing processing time by at least 85%.

Tumor Lysing Genetically Engineered T Cells Loaded with Multi-Modal Imaging Agents

Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert anti-tumor effect by identifying tumor-associated antigen (TAA), independent of major histocompatibility complex. For maximal efficacy and safety of adoptively transferred cells, imaging their biodistribution is critical. This will determine if cells home to the tumor and assist in moderating cell dose. Here, T cells are modified to express CAR. An efficient, non-toxic process with potential for cGMP compliance is developed for loading high cell number with multi-modal (PET-MRI) contrast agents (Super Paramagnetic Iron Oxide Nanoparticles – Copper-64; SPION-64Cu). This can now be potentially used for 64Cu-based whole-body PET to detect T cell accumulation region with high-sensitivity, followed by SPION-based MRI of these regions for high-resolution anatomically correlated images of T cells. CD19-specific-CAR+SPIONpos T cells effectively target in vitro CD19+ lymphoma.

Pharmaceuticals: When to consider revalidating the performance of sterilising grade filters?

Any product or process change has the potential to affect cGMP compliance of a validated system, and the possible sources of change are numerous. Ross W. Acucena, Regulatory Consultant, Services and Solutions with EMD Millipore discusses what needs to be taken into account.

A Risk Assessment Approach: Qualification of a HVAC System in Aseptic Processing Area Using Building Management System

AbstractIn the pharmaceutical industry qualification of HVAC systems is done by using a risk based approach. Failure mode effect analysis (FMEA) concepts were used for risk assessment of a HVAC system to determine the scope and extent of qualification and validation in this present work. The HVAC is the “direct impact” system in the aseptic practice which directly affects the product quality and regulatory compliance. The level of risk associated with the HVAC system was assessed based on the impact and severity of the probable risk in aseptic practice in sterile manufacturing. On completion of the risk assessment, control and measures developed and recommended actions for unacceptable risk were identified for improved cGMP compliance and qualification of the system upgrades. After completion of the risk assessment the recommended actions were extended and verified against the qualification stages of the HVAC system. Finally, the HVAC system was subjected to a performance qualification (PQ) study. All of the tests were performed and a report was generated. On evaluation of the data collected during PQ, it was found that the HVAC system met all the specified design criteria and complied with the entire cGMP requirement. Hence the system stands validated for PQ. Copyright © 2011 John Wiley &amp; Sons, Ltd.

Design and performance evaluation of single-use whole-sterile “plug &amp; play” kits for routine automated production of [11C]choline and [11C]methionine with radiopharmaceutical quality

We herein describe the design and performance evaluation of single-use whole-sterile "plug & play" kits for routine automated production of [(11)C]methionine and [(11)C]choline for human use. Kits were designed for maximal simplicity and ease of using modules from Eckert & Ziegler Modular Lab System. The use of all-disposable sterile medical-grade material, helps ensure safety and cGMP compliance. The quick set-up and removal ("plug & play") also reduces radiation burden to operator.

Adoptive Transfer of CMV-Specific Donor T Cells Following Allogeneic Transplantation Leads to Rapid and Safe Systemic Reconstitution.

Abstract 44Reactivation of CMV remains a significant problem following allogeneic hematopoietic stem cell transplantation. Antiviral drug therapy is effective but toxic, and resistant strains of CMV are increasingly being reported. Virus-specific T lymphocytes are necessary for the control of viral reactivation. Adoptive transfer of donor derived CMV-specific T cells has been reported previously but most methods to produce such cells have involved several weeks of in vitro culture or have produced a therapeutic product restricted to CD8 T cells. The current method involves a short incubation of donor peripheral blood mononuclear cells with either CMV-pp65 protein (20 hours) or a pool of peptides from pp65 (6 hours) with subsequent isolation of interferon-gamma secreting cells by CliniMACS using IFNψ capture microbeads (Miltenyi Biotec). This technique permits rapid isolation of an enriched IFNψ secreting T cell product, manufactured to clinical grade, which is then cryopreserved in dosed aliquots for subsequent infusion. Here we report the outcome of a single arm phase I/II in which CMV-T cells given pre-emptively at first detection (qPCR) of CMV DNA in peripheral blood, or at day +40-60 as prophylaxis. CMV replication was monitored by weekly PCR and reconstitution of CMV-specific T cells by pentamer labelling and/or IFNψ secretion assay. Conventional antiviral drug therapy was instituted if the viral load rose above institutional threshold. 30 recipients of T cell depleted low intensity transplants from HLA-matched CMV-seropositive related donors were enrolled between 2006 and 2008. Donors underwent a second, short apheresis procedure approximately 15 days after collection of the mobilised HPC-A for the collection of CMV-T cells. 26 clinical-grade products were produced to full cGMP standards; four donors were unsuitable or withdrew. The mean yield of cells following enrichment was 41.7% with a median purity of 43.9% (range 1.4-81.8). Adequate CMV-T cells were isolated from all donors. Both pp65 and peptide stimulated products contained both CD4 and CD8 reactive T cells. Median dose of CMV-specific CD4 T cells was 2840/kg and of CMV-specific CD8 was 630/kg. Eighteen patients received a single dose of 1×10^4 CD3+/kg; 13 were CMV seropositive; 11 were treated pre-emptively and 7 prophylactically. 83% had received T cell deplete regimens. Within 2 weeks of infusion in vivo expansion of CMV-T cells was observed in 17 of 18 patients. One patient required 4 weeks to generate detectable CMV-T cell in his peripheral blood. TCR-BV usage of the CMV-T cells post infusion matched that of the cells which had been infused. The 7 patients who had cells infused prophylactically all showed expansions of CMV-T cells in the absence of detectable viral DNA in peripheral blood. Subsequent low level CMV-reactivation was seen in one of these and was associated with rapid CMV-T cell expansion with clearance of virus without anti-viral drug therapy. One developed subsequent extensive chronic GvHD and required antiviral treatment for multiple reactivation episodes following introduction of steroids. Of the 11 patients treated pre-emptively, 9 received antiviral therapy for the initial reactivation, although in 7 patients this was required for only 7-15 days. (compared to a median of 21 days in historical controls). Three patients had a further CMV reactivation event. One followed prednisolone therapy for acute grade II GvHD. The second was the patient who had shown poor T cell expansion post infusion and had required prolonged anti-viral therapy (33 days) for the initial CMV reactivation. The third patient received no treatment and cleared virus following a further in vivo expansion of CMV-reactive T cells, suggesting the presence of a functional memory population. GVHD incidence and severity was no worse than seen in comparable historical controls. 3 patients suffered grade 2-3 acute GvHD. 3/17 evaluable patients developed extensive chronic GvHD (2 were recipients of T replete grafts). 16/18 patients were alive at the end of the 6 month monitoring period and CMV-reactive T cells were detectable in all 16. CMV-specific donor T cells can be readily produced to cGMP compliance which can be safely infused and lead to early immune reconstitution in at-risk patients. Cells expand in response to subsequent CMV-reactivation and patients appear to require fewer anti-viral treatment episodes which is being tested in an ongoing phase III trial. Disclosures:Lowdell:Cell Medica Ltd: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

HPTLC for Quality Control of Traditional Chinese Medicines: Identification and Detection of Adulteration

For cGMP compliance of dietary supplements and quality control of herbal medicinal products, proper identification of herbal raw material is of great importance. In this respect Traditional Chinese Medicines (TCM) can present challenging tasks because pharmacopoeial drug monographs may include multiple species and often don't provide sufficient analytical methods. High Performance Thin-Layer Chromatography (HPTLC) is a very suitable tool for direct comparison of fingerprints from multiple samples side by side and allows determining similarities and differences of related species. Using “BEIMU” (Fritillaria spp.) and “CANGZHU” (Atractylodes spp.) as examples, the development and use of validated methods for this purpose is illustrated. The traditional approach of associating the quality of an herbal medicine with the quantity of a marker becomes questionable, if the product contains more than one plant material. CANGZHU XIANGLIAN SAN a TCM for veterinary use contains Coptis rhizome, Aucklandia root, and Atractylodes root but the Chinese Veterinary Pharmacopoeia only relies on identification and quantitation of berberin as principal marker. Berberin is present in Coptis only. This creates the possibility for adulterated products, missing either of the other two plants to enter the market. We propose an HPTLC method that allows a more complete monitoring of quality by ensuring the presence of all species in the appropriate quantity.

The impact of cGMP compliance on consumer confidence in dietary supplement products

The FDA estimates that US citizens spend more than $ 8.5 billion a year on dietary supplements and world wide the market is estimated at more than $ 60 billion. However, although a majority of consumers express confidence in the safety of these products, 74% believe the government should be more involved in ensuring that these products are safe and efficacious. Recent regulatory initiatives such as the imminent adoption of cGMPs for dietary supplements in the US, implementation of cGMPs in Canada and the recent EU dietary supplement initiative represent legislative and industry response to public clamor for more comprehensive oversight of dietary supplements. Regardless of mandated practices, the majority of dietary supplement manufacturers have done an excellent job of protecting the safety and quality of their products. The promulgation of these cGMPs will help ensure consumers that equal standards are followed throughout the industry. For some companies with established processes based on existing food or pharmaceutical cGMP regulations, the transition will be relatively painless while, for many, it will represent a significant increase in the level of documentation and testing. However, consumers deserve and demand that products meet standards for safety and quality and the implementation of cGMPs for these products are an important first step. Although the cGMPs are designed to ensure products are safe from a standpoint of identity, purity, quality, strength and composition, they do not address preclinical or clinical testing of ingredients for safety or efficacy. This would involve ingredients meeting the requirements of Generally Recognized as Safe (GRAS) status or going through the New Dietary Ingredient (NDI) process.