Drug Master Research Articles

Regulatory requirement and filling procedure of drug master file in India under central drug standard control organization (CDSCO) in comparison with South Korea

The Drug master file (DMF) is a type of Confidential file that submitted to regulatory authorities about the ingredients, process, packing and storage of any drugs intended to human use. Drug master file plays an important role in production of drug. The Indian regulatory agency is a CDSCO that manages and encourage DMFs in India and in South Korea MFDS manages the DMFs. Unveiling the difference in regulatory requirements and filling procedure of DMF in India and South Korea as per CDSCO and MFDS respectively. Make certain the Protection, Grade, and Effectiveness of Drug Products.

Microwave-assisted green synthesis and molecular docking study of some new 4-thiazolidinone derivatives as possible bioactive agents

We have developed an economical and environmentally friendly microwave-assisted efficient method for the synthesis of a series of new 4-oxo-thiazolidine derivatives (4a-d). The method involves microwave irradiated cyclocondensation reaction of Schiff bases (3a-d) and thioglycolic acid in drug master file (DMF). 4-oxo-thiazolidine derivatives (4a-d) was also synthe 4-Oxo-Thiazolidine derivatives were also synthesized by conventional heating procedures and consequence were Compared with Microwave assisted green method. The results suggest that microwave-assisted syntheses lead to higher yields within very short reaction times. Antimicrobial screening of all the synthesized compounds was carried out using Gram-positive strains Staphylococcus aureus and Gram-negative strain encompassing Escherichia coli, Proteus vulgaris, and Salmonella typhi. The results were compared with the standard drug chloramphenicol. All the synthesized compounds were subsequently examined using molecular docking experiments against peptide deformylase (PDB ID: 1G2A), which evaluates the binding interaction of ligands with enzyme active sites.. KEYWORDS :Microwave irradiation, Thiazolidinone, Molecular docking, Peptide deformylase, Antimicrobial screening.

A Review Process of ANDA Filling in PMDA (Japan) and Calibration of UV in Accordance to its Regulatory Guidelines

The Abbreviated New Drug Application (ANDA) filing system is an important regulatory process in Japan for the approval of generic drugs. This system allows pharmaceutical companies to submit an application for the marketing and sale of a generic drug, which has already been approved by the regulatory agency in another country. The ANDA system in Japan is similar to that of the United States and Europe, but there are some unique aspects that must be taken into account. For example, in Japan, the regulatory agency requires a separate drug master file for each active pharmaceutical ingredient, which can be a time-consuming process. UV spectrophotometry is a widely used analytical technique for the characterization of pharmaceuticals, including active pharmaceutical ingredients and finished dosage forms. The Shimadzu UV-1800 spectrophotometer is a popular instrument for this purpose, which is widely used in Japan. This instrument has a range of features that make it particularly useful for pharmaceutical analysis, including a wavelength range of 190-1100 nm, a double beam optical system, and a low stray light level. The Shimadzu UV 1800 is also compatible with a range of accessories, such as a multicell holder, which allows for the simultaneous measurement of multiple samples. The combination of the ANDA filing system and UV spectrophotometry using the Shimadzu UV-1800 is an important tool for the development and approval of generic drugs in Japan. The ANDA system allows for a streamlined regulatory process for generic drug approval, while UV spectrophotometry provides a reliable and accurate method for the characterization of pharmaceuticals. Together, these tools help to ensure the safety and efficacy of generic drugs in Japan.

A U.S. Food and Drug Administration perspective on cannabis research and drug development

Since the early 1970s, the U.S. Food and Drug Administration (FDA) has received over 800 investigational new drug applications (INDs) for, and pre-INDs pertaining to, research of cannabis or cannabis-derived products. The current data show that applications for research of these products submitted by both academic researchers and commercial developers focus on four major clinical areas: addiction and pain medicine (53%), neurology (19%), immunology and inflammation (14%), and psychiatry (9%). The product types studied have expanded greatly in recent years and include a wide variety of topical, inhalable, injectable, and oral products. In this article, the authors present a breakdown of cannabis and cannabis-derived applications received by the FDA over the past 50 years. The authors also provide a summary of their experience and challenges in reviewing applications for research of cannabis and cannabis-derived products, as well as recommendations for those interested in studying cannabis and cannabis-derived products in human clinical trials. This perspective article includes a discussion on important IND criteria, the pre-IND consultation program, drug master files (DMFs), and various guidance documents and resources. Lastly, the authors provide their perspective for the future of cannabis drug development.

Similarities and differences in filing for Drug Master File in US, Canada and Europe

Drug Master File or DMF is a document prepared by a pharmaceutical manufacturer and submitted solely at its discretion to the applicable authority in the intended drug market. The document provides the non-supervisory authority with confidential, detailed information about installations, processes, or papers used in the manufacturing, processing, packaging, and storing of one or further mortal drugs. The DMF form allows an establishment to cover its intellectual property from its mate while complying with non-supervisory conditions for exposure of processing details. There is no non-supervisory demand to file a DMF. Drug Master Files (DMF) is a document containing complete information on an Active Pharmaceutical element (API) or finished drug capsule form. Though there are no non-supervisory conditions to file a DMF, the benefit of its use is inviting. A drug Master Files (DMF) is an voluntary non-supervisory submission and is submitted at the discretion of the DMF holder to help their guests. A DMF is NOT a cover for an IND, NDA, ANDA, or Export Application. It is not approved or disapproved. An Active Substance Master File (ASMF) is the presently honored term in Europe, formerly known as European drug Master file (eDMF) or a US- Drug Master File( US- DMF) in the United States.

Automation of the medication process in Swiss hospitals: results of a survey

ObjectivesMedication management is a core process in hospital administration. The safety, timeliness and efficiency of medication distribution may be improved by automating logistical and administrative aspects of the process. Forming...

Clinical Radiosynthesis and Translation of [18F]OP-801: A Novel Radiotracer for Imaging Reactive Microglia and Macrophages.

Positron emission tomography (PET) is a powerful tool for studying neuroinflammatory diseases; however, current PET biomarkers of neuroinflammation possess significant limitations. We recently reported a promising dendrimer PET tracer ([18F]OP-801), which is selectively taken up by reactive microglia and macrophages. Here, we describe further important characterization of [18F]OP-801 in addition to optimization and validation of a two-step clinical radiosynthesis. [18F]OP-801 was found to be stable in human plasma for 90 min post incubation, and human dose estimates were calculated for 24 organs of interest; kidneys and urinary bladder wall without bladder voiding were identified as receiving the highest absorbed dose. Following optimization detailed herein, automated radiosynthesis and quality control (QC) analyses of [18F]OP-801 were performed in triplicate in suitable radiochemical yield (6.89 ± 2.23% decay corrected), specific activity (37.49 ± 15.49 GBq/mg), and radiochemical purity for clinical imaging. Importantly, imaging mice with tracer (prepared using optimized methods) 24 h following the intraperitoneal injection of liposaccharide resulted in the robust brain PET signal. Cumulatively, these data enable clinical translation of [18F]OP-801 for imaging reactive microglia and macrophages in humans. Data from three validation runs of the clinical manufacturing and QC were submitted to the Food and Drug Administration (FDA) as part of a Drug Master File (DMF). Subsequent FDA approval to proceed was obtained, and a phase 1/2 clinical trial (NCT05395624) for first-in-human imaging in healthy controls and patients with amyotrophic lateral sclerosis is underway.

Digitalisation of the drug prescribing process in Swiss hospitals – results of a survey

BackgroundThe state of digitalisation in the healthcare sector in Switzerland is lagging, even as the national electronic health record (EHR) is being gradually implemented. Little is known about the implementation...

Scientific Considerations for Stability Studies of Drug Substances Supporting Abbreviated New Drug Applications (ANDAs).

We have summarized five high impact issues related to the stability studies for drug substances that are documented in the Type II drug master files (DMFs) supporting Abbreviated New Drug Applications (ANDAs). We intend to provide the scientific considerations for the regulatory policies which bear upon such high-impact issues. We have also provided our perspective to avoid such issues, to reduce the DMF review time, and subsequently to accelerate the approvals of the supporting ANDAs.

Assessment of Regulatory requirements and filing procedure of Drug Master File for Brazil, Europe and South Africa

A Drug Master File is a record that consists of detailed, correct data approximately an Active Pharmaceutical Ingredient (API) or Dosage Form of a Finished Product (FP). It is a classified document containing thorough, accurate, and up-to-date information regarding the active medicinal ingredient and medicament. A DMF is divided into two sections: (a) Open part (the Applicant's Part), which includes all of the details needed to determine the quality of a product. And (b) the Closed Part (Restricted Part). The Restricted Part (Closed Part) comprises openly undisclosed manufacturing method knowledge only given to authorized individuals. This compilation aims to offer a comparison of DMF regulatory necessities in addition to the exact data for the registration of lively pharmaceutical ingredients (API) for common drugs in various regulatory governments, including EUROPE (EDQM, EMA), BRAZIL (ANVISA), and SOUTH AFRICA (SAHPRA). This review will provide information on the differences and similarities in the DMF filing requirements in EUROPE, BRAZIL, and SOUTH AFRICA. The regulatory criteria for API registration vary by jurisdiction. Despite the existence and widespread adoption of an ICH-CTD standard format, there are also some limitations. There are a few particular requirements set provided to drug authorities along with the submission. The registration procedure is a regulatory undertaking that permits a person/organization/sponsor/innovator to get permission to participate in the regulation process for fetching marketing authorization/approval.

A Review on DMF Filing in EU, USA and Australia

Drug master file (DMF) is highly confidential information describing the aspect elements and error free information regarding API and finished dosage form. It consists of two parts. One is open part and another one is restricted part. Open part contains the information about the quality of drug product by the licence holder. Prohibited part which is Closed part which is protect the secret and unofficial information about manufacturing of product which is relived In front of respect regulatory authorities. When two or more persons involved in manufacturing of pharmaceutical. The drug master file contains overall information about product quality, maturing stability and purity of the medicaments. Drug master file gives the support to the IND (Investigational New Drug) application, ANDA (Abbreviated New Drug Application), NDA. Every country has its own drug filling format and content. The current observation is different countries drug master filing, content of drug master filing and format of the filing respect countries.

Meeting Report: N-Nitrosamine Impurity Control Strategies in the Pharmaceutical and Biotechnology Industries

The American Association of Pharmaceutical Scientists (AAPS) Chemistry, Manufacturing, and Control (CMC) Community hosted a virtual panel discussion on December 9, 2020, to provide a forum to discuss N-nitrosamine control strategies in the pharmaceutical and biotechnology industries. The panel included staff from the US Food and Drug Administration (FDA) and industry subject matter experts. Meeting topics included acceptable intake levels for nitrosamine impurities, definitions of "acceptable level of risk," water as a contributor in nitrosamine risk assessments, nitrosamine impurity control strategies based upon fate/purge data, early vs. late development assessment expectations, application to oncology programs developed under ICH S9, and Drug Master File (DMF) regulatory expectations. During the meeting, divergence in global health authority expectations was additionally discussed. One of the most important outputs from this AAPS panel discussion was the criticality of continued dialog between industry and health authorities to help understand actual versus perceived risks and provide pragmatic, scientifically justified solutions to ensure patients are provided with an uninterrupted supply of safe medicines based on globally harmonized requirements.

Oral health status and microbial load of Streptococcus mutans in children with Cerebral palsy in a tertiary care hospital in Delhi.

Cerebral palsy (CP) is a childhood debilitating condition which impairs the physical and mental ability of an individual to maintain oral health. The objective of the present study was assessment of dental neglect and burden of treatment needs of children affected with CP as compared to normal children in a tertiary care hospital in Delhi. A sample size of 104 children of age group of 6-14 years was selected, in which 52 children of CP (case group) and 52 normal school children (control group) were recruited. Children from both groups were examined, and calculation of drug master files (DMFS), defs, oral hygiene index (OHI), and gingival index was done. The presence of trauma and malocclusion was assessed. Present caries activity was assessed by the level of Streptococcus mutans present in saliva in both groups. Treatment needs were then assessed based on intraoral findings. Data were analyzed by SPSS 20.0 software. Student's t-test and nonparametric statistical tests such as Chi-square test and Mann-Whitney test were used as per the nature of variables studied for statistical analysis with the level of significance denoted at P < 0.05. The mean DMFS, gingival index, OHI, and treatment needs were observed to be higher in the CP group. Increased S. mutans levels were observed in saliva of CP patients. Defs score, trauma, and malocclusion were not statistically significantly higher in CP group as compared to the control group. Cerebral palsy group had a poor oral and gingival health, a higher DMFT and burden of treatment needs and an increased risk of further caries progression due to high caries activity indicated by increased level of salivary Streptococcus mutans than the control group.

Filing of DMF in the US, EU, and India, and its comparative review

A Drug Master File (DMF) covers all comprehensive, accurate, and precise information about Active Pharmaceutical Ingredient (API) or Finished Product Dosage Form (FP). It is a confidential document that contains complete, factual, and correct information about the active pharmaceutical ingredient and drug product's chemistry, manufacture, stability, purity, impurity profile, packaging, and the cGMP (Current Good Manufacturing Practices) status of any human drug product. When a DMF is filed, it allows a company to safeguard its intellectual property from its partner while complying with regulatory requirements when its process details are disclosed. There is no legalised or regulatory requirement to file a DMF. A DMF comprises of two parts: (a) the Applicant's Part (Open Part), which contains all the information to assess the quality that the license-holder requires and submit a license or amendment application; and (b) the Restricted Part (Closed Part), which contains confidential information about the manufacturing procedure which is only disclosed to the authorities.&#x0D; A DMF can be used by a holder who establishes the file or by one or more parties to support their files or applications.&#x0D; The present study is to brief an overview of DMF filing in different countries, which are the USA, Europe, and India. It also gives information on regulatory requirements of Drug Master Files by Food and Drug Administration (USA), European Medicines Agency (Europe), and Central Drug and Standard Control Organization (India) and their comparison.

Contextual influences of illicit adolescent marijuana cultivation and trading in the Inqguza Hill local municipality of South Africa: implications for public health policy

BackgroundAlthough commercial cultivation and trading of marijuana, commonly known as cannabis or dagga in the South African context, remains an illicit practice, adolescents actively engage in it. However, contextual influences that sustain adolescent involvement in illicit marijuana-related activties remain empirically unascertained.ObjectiveThis study sought to ascertain the various contextual influences of adolescent illicit marijuana cultivation and trading in two communities in the Ingquza Hill Local Municipality (IHLM) of South Africa, using the tenets of the Socio-Ecological Model (SEM).MethodsThe study utilised focus group discussions approach to interview thirty-three purposefully sampled participants who were recruited through the snowball sampling technique. A semi-structured interview guide was used to conduct the interviews, while thematic content analysis was used to analyse the data.ResultsWe found that illicit adolescent marijuana cultivation and trading was influenced by eleven contextual factors that are grouped under four levels of socio-ecological influence. These include intrapersonal influences (knowledge and skills in marijuana cultivation and courage), interpersonal influences (peer and family influences), communal level influences (economic reasons, early childhood exposure to marijuana activities, protection of family lands, the topography of the area and soil fertility) and policy-related influences (lack of communal bylaws on marijuana activities and laxity in law enforcement).ConclusionIt is recommended that substance abuse prevention policies and programmes focus on discouraging children from engaging in illicit marijuana activities in IHLM across the four tenets of SEM and curtailing adolescent involvement in marijuana cultivation and trading. There is also the need to incorporate the law enforcement approach into demand reduction strategies of the National Drug Master Plan (NDMP), which employs only an educative approach in its current form. Working agreements between municipal authorities, law enforcement agents and social service professionals also need to be strengthened to push demand reduction strategies for marijuana in communities to protect the rights of children as enshrined in the Children’s Act, 38 of 2005.

Opportunities, Constraints and Critical Supports for Achieving Sustainable Local Pharmaceutical Manufacturing in Africa: With a Focus on the Role of Finance, Final Report

The Open Society Foundations Public Health Program commissioned an interdisciplinary team to examine the extent to which gaps in financing are an obstacle to more robust local production of pharmaceutical products (including diagnostics, vaccines and treatments (DVT)) and personal protective equipment (PPE) with focus on Africa. The Report is posted here. The Executive Summary and an Addenda compilation (which includes 3 supplemental research reports) are posted along with the Report at the website of Nova Worldwide Consulting.The overall findings of the study are that gaps in financing pose a constraint on the localization of pharmaceutical production in Africa. The gaps are not mainly due to a lack of financial capital in global financial markets that might be deployed for this purpose. The main problems are associated with the market environment in the sense that sustainable business operations require adequate demand, and market demand for pharmaceutical products in Africa is limited by various factors. In addition, comparatively weak infrastructure (recognizing variation among countries) makes it difficult to compete with large efficient foreign suppliers that are bolstered by foreign government support. Potential investors appear to perceive relatively high risks associated with investing in pharmaceutical manufacturing in Africa.Transforming political engagement:The COVID-19 pandemic may serve as adequate impetus to transform local production of pharmaceuticals into a governmental priority. Government commitment at a high level is required to engage the financial levers that will support localization of production.Sustainable business models:Particularly outside the vaccine sector, successfully operating a pharmaceutical manufacturing facility means addressing a market with sufficient demand to generate revenue and profits. Alternatively, or as a supplement, governments may provide direct subsidies, guaranteed offtake agreements, tax credits, local production pricing premiums, and other measures to substitute for market demand. These forms of support are commonly used for “infant industries”, and there should be plans to withdraw such support once a business has achieved sustainability.The social impact investor market:African governments should consider a program to encourage sovereign wealth funds and other financial asset managers to invest in local production on the African continent as a way to accomplish important social goals. To facilitate this objective, there should be some type of backstop or guarantee of the social impact investments within reasonable parameters. The African Development Bank may be helpful in establishing mechanisms for this purpose.Opportunities for advocacy:There is substantial room for advocacy by civil society to move Africa toward greater self-sufficiency in the production of pharmaceutical products. At the high level of political commitment, government authorities should be persuaded to prioritize local production of pharmaceuticals as a matter of public health security, engaging the financial levers to support such a commitment. At the level of industrial policy, the African Union should be encouraged to engage in concrete planning for regional pharmaceutical production hubs, and associated infrastructure and centers of technical expertise. Whether in conjunction with that, or separately, procurement authorities should be encouraged to form regional pooled procurement mechanisms to aggregate demand, allow for more effective bargaining with suppliers, and support regional hub manufacturers.Support for effective implementation of the African Continental Free Trade Area in terms of reducing barriers to intra-Africa trade in pharmaceutical products would improve the market situation. Similarly, continuing support for efforts to integrate the African regional regulatory structure for pharmaceutical products would accelerate access to medicines. Establishment of a library of available drug master files for reference by manufacturers would significantly lower barriers to manufacturer market entry.Foundations should be encouraged to develop a transparent platform which could provide information to African manufacturers with respect to opportunities for financing and expertise for pursuing their objectives.

Evaluating and understanding the outcomes of the South African National Drug Master Plan 2013–2017: A systems‐based integrative propositional analysis application

AbstractA balanced approach using an integrated combination of strategies, namely, demand reduction, supply reduction and harm reduction, was suggested to be implemented in a balanced way to the policy vision of a South Africa ‘free of substance abuse’. Responding on the call for a comprehensive review of the National Drug Master Plan 2013–2017 to ensure consistency in policy approach, this article explores the integrative propositional analysis (IPA)‐based analysis to evaluate ‘how systemic’ and integrated were the policy strategies applied. The analysis draws insights from the internal consistency of the policy and provides complementary evidence on the systemic breakdown of the policy, which correlates with previous studies. The findings are indicative of the usefulness of the IPA‐based tools to more pragmatically develop policy that better reflects the systemic/integrated relationship of the three strategies based on their conceptual systemic integrity. This research has implications for interdisciplinary scholars and practitioners, of policy and theory.

Novel Clinical Trial Designs and Statistical Methods in the Era of Precision Medicine

After an overview of FDA’s draft guidances to industry on adaptive designs and enrichment strategies for clinical trials, we describe recent advances in adaptive confirmatory trial designs and statistical methods for their analysis. We then focus on biomarker-guided personalized therapies in the era of precision medicine, and precision-guided drug development and master protocols, and conclude with innovations in statistical science for precision medicine and regulatory submission.

Non‐Aqueous Phospholipid Concentrates for Increasing the Bioavailability of Poorly Soluble Compounds

AbstractThe properties and use of liquid non‐aqueous phospholipid concentrates (NAPC) are reviewed. They are mainly used to solubilize poorly water‐soluble drug substances to enhance their oral bioavailability, but they also find applicability in dietetics and cosmetics. Due to the large‐scale availability of these concentrates at good manufacturing practice quality including Drug Master File (DMF) documentation, they can be used for pre‐clinical screening and clinical testing and as market form, as demonstrated by the product of Wyeth/Pfizer, Rapamune, enabling a cost effective and fast dosage form development. When needed, NAPC can be converted to solid dosage forms by means of a capsule fill or addition of adsorbing excipients. It is concluded that NAPC deserve more attention and a broader use in the life science industry.Practical Applications: NAPCs are suitable as pre‐clinical formulation vehicle for screening of the oral bioavailability of poorly water‐soluble compounds. The same formulation can be used for clinical testing and market introduction, allowing a fast track dosage form development. When needed NAPC can be converted to solid dosage forms. NAPC have also applicability in dietetics and cosmetics to solubilize poorly water‐soluble compounds.

Comparison of Regulatory Requirements for Filing Drug Master File (DMF) in Emerging Markets - China, Brazil &amp; South Korea

Background: A DMF consists of confidential information, usually related to Chemistry, Manufacturing and Control (CMC) of the drug substance. DMF is prepared and submitted by the pharmaceutical manufacturer solely to the regulatory authority of the respected country where he wants to market. Objective: Compare the regulations of the emerging markets with that of a regulated market and to highlight the stringent requirements imposed by emerging authorities. The similarities and differences of the requirements for filing a DMF in emerging markets are compared against the regulated market. Methods: The method carried out for every single study follows some patterns and certain pathways in order to reach its target. Method begins with scope and objective of regulatory perspective of DMF filing requirements for USA, China, Brazil and Korea. The information was collected from Regulatory authorities, Legislations, Guidelines and Experts opinion. Results: Regulatory requirements for filing a DMF for API registration vary from country to country. Even though a standard ICH-CTD format is available and most widely followed, there are some specific requirements recommended by drug authorities which are mandatory to be provided while filing to that particular country. Conclusion: Based on the current study it is clear that emerging markets possess more stringent requirements for API approval as compared to the regulatory market but the dispute is that the emerging markets do not have harmonized guidelines and are not transparent enough.