FDA: Compliance | Regulations | DMF | Submission | Process | الامتثال: لوائح إدارة الغذاء والدواء الأمريكية | الملف الرئيسي للأدوية | تقديم | عملية

 

A Drug Master File (DMF) is a submission to the US Food and Drug Administration (FDA) that contains information about a specific aspect of a drug product, such as the manufacturing process, raw materials, or analytical methods. DMFs are used to provide confidential information to the FDA that is relevant to the safety and effectiveness of a drug product, but that the sponsor of the drug does not want to disclose publicly.

There are three types of DMFs:

Type I DMFs contain information about the facilities, processes, or articles used in the manufacturing, processing, packing, or holding of a drug product.

Type II DMFs contain information about the composition, manufacturing, and testing of drug substances (also known as active pharmaceutical ingredients or APIs).

Type III DMFs contain information about the stability of a drug product.

The steps in the Drug Master File (DMF) submission process are as follows:

Preparing a DMF submission: The sponsor of the drug (usually the manufacturer or developer) prepares a DMF submission that includes all of the required information and documentation. This may include details about the facilities, processes, or articles used in the manufacturing, processing, packing, or holding of the drug product, as well as information about the composition, manufacturing, and testing of drug substances (for Type II DMFs) or the stability of the drug product (for Type III DMFs).

Submitting a DMF to the FDA: The sponsor submits the DMF to the FDA through the Electronic Submission Gateway (ESG), along with a cover letter and any required fees.

FDA review of a DMF submission: The FDA reviews the DMF submission to ensure that it is complete and meets all regulatory requirements. If the FDA determines that the DMF is acceptable, it will be filed and made available to other parties (such as other manufacturers or developers) who may want to reference the information in their own submissions. If the FDA determines that the DMF is not acceptable, it will provide the sponsor with feedback on how to correct any deficiencies.

It is important to note that the DMF submission process can be a lengthy and complex process, and it is not uncommon for multiple rounds of review and revision to be required before a DMF is accepted by the FDA.

Maintenance of a DMF

To maintain a DMF, it is important to keep the information it contains up-to-date and accurate. This may involve regularly reviewing and updating the DMF to ensure that it accurately reflects the current state of the component, drug substance, drug product, or excipient. It may also involve submitting updates or amendments to the DMF to the FDA as needed.

In addition to maintaining the accuracy and completeness of the information in a DMF, it is also important to protect the confidentiality of the DMF. This may involve implementing appropriate security measures to prevent unauthorized access to the DMF and ensuring that only authorized personnel have access to the information it contains.

Overall, the maintenance of a DMF is an important part of ensuring the quality, safety, and efficacy of drug products and ensuring compliance with regulatory requirements.

There are several benefits to the DMF process for both manufacturers and regulatory authorities. 

Some of the key benefits of the DMF process include:

Access to information: DMFs provide manufacturers, importers, and other interested parties with access to information about the quality, safety, and efficacy of specific components, drug substances, drug products, or excipients used in the manufacture of drug products. This can help to ensure that these components meet appropriate standards and can be used safely and effectively in the manufacture of drug products.

Streamlined drug development: By submitting a DMF, manufacturers can provide regulatory authorities with information about specific components, drug substances, or excipients that can be referenced in the review of a new drug application (NDA). This can help to streamline the drug development process and reduce the need for additional testing or data submission.

Confidentiality: DMFs are confidential submissions to regulatory authorities and are protected from disclosure under the Freedom of Information Act (FOIA). This can help to protect the proprietary information of manufacturers and encourage the submission of high-quality, comprehensive DMFs.

Quality assurance: The DMF process helps to ensure the quality and consistency of drug products by providing regulatory authorities with information about the components, drug substances, or excipients used in their manufacture. This can help to ensure that drug products meet appropriate standards and are safe and effective for use.

Overall, the DMF process provides a number of benefits to manufacturers and regulatory authorities, helping to ensure the quality, safety, and efficacy of drug products and streamline the drug development process.

The drug master file (DMF) process can present several challenges for pharmaceutical companies. 

Some of the common challenges include:

Complexity of the process: The DMF process can be complex and time-consuming, requiring a detailed understanding of regulatory requirements and the submission process.

Resource constraints: Preparing a DMF requires a significant amount of time and resources, including personnel with specialized knowledge and expertise. This can be a challenge for smaller companies with limited resources.

Confidentiality concerns: DMFs contain confidential and proprietary information, which can make it difficult to share with regulatory agencies and other stakeholders.

Ensuring compliance: It is important to ensure that DMFs are complete, accurate, and compliant with regulatory requirements. This can be challenging, especially for companies with limited experience with the DMF process.

Changes to regulatory requirements: Regulatory requirements can change over time, which can impact the DMF submission process and require companies to update their DMFs to remain compliant.

Managing multiple DMFs: Companies that have multiple products may need to prepare and maintain multiple DMFs, which can be a logistical challenge.

Overall, the DMF process can be challenging for pharmaceutical companies, but it is an important part of the drug development process and ensures that the safety and effectiveness of the drug are thoroughly evaluated by regulatory agencies.

In conclusion, the drug master file (DMF) process plays a critical role in the drug development and approval process. DMFs provide regulatory agencies with information about the manufacturing, control, and distribution of drugs, helping to ensure that these products are safe and effective for use by the public. While the DMF process can be complex and challenging, it is an important step in ensuring the quality and safety of pharmaceutical products. Some of the potential benefits of the DMF process include providing regulatory agencies with important information about a drug, helping to facilitate the approval process, and providing transparency about the manufacturing and control of a drug. However, the DMF process can also present challenges, including the complexity of the process, resource constraints, confidentiality concerns, and the need to ensure compliance with regulatory requirements. Overall, the DMF process is an important part of the drug development process and helps to ensure that pharmaceutical products are safe and effective for use by the public.

TGA: Approved | Paxlovid | Lagevrio | السلع العلاجية في أستراليا: تمت الموافقة عليها | باكسلوفيد

Australia will before long be outfitted with another weapon in the battle against Covid yet it is likewise expected to be the following thing hit by deficiencies.

Oral prescriptions for Covid-19 are relied upon to be hard to come by in Australia for the initial not many months after the medications controller gave them the go-ahead.

The Therapeutic Goods Administration recently conceded provisional approval to Pfizer's Paxlovid and Merck Sharp and Dohme's Lagevrio for use in the country.

The central government has requested approximately 800,000 portions of the antiviral pills, with the first shipments due to show up in quite a while.

In any case, Royal Australian College of General Practitioners President Karen Price said there was an overall deficiency of the meds which would add to supply requirements in Australia.

"They're coming very soon. I would think inside this month we'll have some accessibility. In any case, I figure expanded accessibility will be a couple of months down the track," she told Sydney 2GB radio.

"Like these things in Covid, there will be introductory energy and afterward there will be dissatisfaction since they're coming in little numbers.

"We are guaranteed those bigger numbers later on, yet when is a decent inquiry."

The medicines are not relied upon to open up until they are recorded on the PBS and have their expenses financed by the Australian government, Dr Price said.

"As far as getting them on the Pharmaceutical Benefits Scheme (PBS) and going to the scientist to get them, that might be a couple of months down the track," she said.

"They will not be on the PBS, so as a GP we'll be holding on to see. We need to go through the public reserve, I see, so there'll be some drivel in attempting to get them."

Taken inside five days of indications, the pills are intended to stop the infection becoming extreme in gentle and direct cases.

Dr Price said the prescriptions wouldn't be appropriate for everybody and that they were "by no means" a substitute for the antibody.

"It'll be for the individuals who are at extremely high danger of advancing onto serious Covid and that might mean individuals with other persistent ailments, etc.," she said.

"These are actually one more reinforcement for those individuals specifically who are unvaccinated. (Yet, getting immunized is simply the method for keeping from getting serious Covid and winding up in clinic or more terrible."

The temporary approval of the Paxlovid and Lagevrio in Australia is dependent upon specific severe conditions, for example, the prerequisite for the sponsors to keep giving data to the TGA on longer-term adequacy and security from progressing clinical preliminaries and post-marketing assessment.

The two medications have gotten restrictive marketing authorization from the UK medicines regulator and emergency use authorization from the US Food and Drug Administration.

Paxlovid was approved for use by Health Canada prior in January.

 

FDA: Approved | SANCUSO | إدارة الغذاء والدواء: معتمد | سانكوسو

SANCUSO is the first and only FDA-approved prescription patch for the prevention of nausea and vomiting in patients getting particular sorts of chemotherapy therapy.

The active medication in SANCUSO, granisetron, gradually disintegrates in the slender layer of adhesive that adheres to the patient's skin and is delivered into their circulatory system more than a few days, working ceaselessly to prevent chemotherapy-induced nausea and vomiting (CINV).

It is applied 24 to 48 hours prior to getting chemotherapy and can prevent CINV for up to five continuous days. Elective oral medicines should be taken a few times (constantly) to convey similar remedial dosages. "In 2020 there were almost 2,000,000 new instances of disease in the U.S.

What's more every year over a large portion of 1,000,000 Americans go through chemotherapy, with many experiencing the symptoms of their treatment. With SANCUSO, patients are given a basic, simple to apply protection arrangement that doesn't need gulping any pills which can be hard for patients encountering queasiness," said, CEO at Cumberland Pharmaceuticals. "We are respected to assume liability for the brand and present it through our business association, guaranteeing that it is conveyed to the patients who need it."

Under the particulars of the arrangement, Cumberland will obtain U.S. Rights to SANCUSO and will accept full business accountability for the product including its marketing, promotion, distribution, manufacturing and medical support activities.

Net sales of the brand in the U.S. Were more than $14 million out of 2020. The financial terms of the procurement incorporate a $13.5 million installment to Kyowa Kirin after shutting, up to $3.5 million in achievements and layered sovereignties of up to 10% on U.S. Net product deals.

Kyowa Kirin will hold international rights, proceeding to convey the product to address oncology patients' necessities all through the remainder of the world. "Since its send off in 2008, we have set up SANCUSO as a significant strong helpful answer for oncology patients the nation over," said, president of Kyowa Kirin North America. "We accept that Cumberland is all around situated to upgrade the worth of the brand and guarantee that this extraordinary item keeps on conveying significant helpful advantages to oncology patients."

 

Active Pharmaceutical Ingredients: Manufacturing | End-User | المكونات الصيدلانية الفعالة: من التصنيع إلى المستخدم النهائي

The SME Pharma Industries' Confederation (SPIC) has said that thinking about the expanding cost of active pharmaceutical ingredients (APIs) and excipients, the maximum price tags of measurements type of medications ought to be permitted to shift couple with the ingredient cost every once in a while. 

During the most recent few months, the costs of mass medications have soar which is uncommon, said, secretary general, SPIC. 

For example, the cost of paracetamol has jumped from Rs. 350 for each kilogram pre-covid period to Rs. 900 for every kg as of now, cost of anti- epileptic medication carbamazepine from Rs. 2,000 to Rs. 5,500 for every kg, anti-biotic ceftriaxone sterile and tazobactam increased from Rs. 6,600 to Rs. 8,200 and Rs. 47,000 to Rs. 55,000 individually. Spray, an excipient for tablets has seen the costs going up from Rs. 500 for each kg to Rs. 750 for each kg and aluminum foil for rankling of tablets from Rs. 325 to Rs. 525 from pre Covid periods to the current occasions. 

The maximum price tags of measurement structure drugs are not changed on schedule by the National Pharmaceutical Pricing Authority (NPPA) in any event, when the expense of natural substance of medication surpasses the maximum cost of medication. NPPA has been dormant when the costs of API have soar, which is bringing about decay of value. With the interest staying high for specific measurements structure drugs and the genuine makers not ready to create the medication taking into account fixed maximum cost, there is inspiration for secret components to make up for the shortfall, he said. 

"The present moment the circumstance is the most noticeably awful ever. Authentic producers are losing portion of the overall industry and getting debilitated," he said in a letter addressed to Prime Minister Narendra Modi. The affiliation has been, over the most recent 10 years, reminding the public authority about the risks of reliance on China, particularly when it is an adversary and forceful neighbor. 

He claimed that the bulk pharmaceutical wholesalers have been accumulating sure unrefined components and making a fast buck taking into account nonappearance of any administration strategy to abridge them. CDSCO can assume a major part in this viewpoint as the conditions are outstanding. 

"While bulk pharmaceutical wholesalers are permitted to opportunist by storing, the little units endure on the grounds that piece pharma likewise corners the accessible amounts of bulk medications," he said. 

"Except if the API costs are likewise brought under value control, the maximum price tags of dose structure medications ought to be permitted to change as indicated by API cost every now and then. Government needs to guarantee anticipation of the current discomfort as recorded above if reasonable quality generics are to be given to its populace and to the remainder of the world,” he added.

 

Pharmaceutical Industry: Regulatory Affairs | India | دور الشؤون التنظيمية في صناعة الأدوية في الهند

The proposed reforms in the existing drug regulatory system, including allowing manufacturing and stockpiling of non-COVID vaccines while witnessing clinical trial. the Health Ministry's May 18, 2020, review announcement, saying it allowed manufacturing and stockpiling of COVID- 19 vaccine under clinical trial for marketing authorization for trade or distribution.

Because of this rule, it came possible for manufacturing and stockpiling the COVID- 19 vaccine during the clinical trial and they could make the vaccine available in such a short span of time to cover millions of lives.

By the end of 2020, SII( Vaccine Manufacturer) has formerly produced around 50 million tablets of the Oxford- AstraZeneca COVID- 19 vaccine" Covishield", indeed while it awaited the medicines Controller General of India'' s( DCGI) nod for exigency use of its vaccine in the country.

In view of the successful result of this provision for COVID- 19 vaccine, this provision should also be enforced fornon-COVID-19 vaccines, of authorization to use the remaining amounts of batches of COVID and non-COVID vaccines for marketable purpose which have been used in a clinical trial.

In this environment, the Health Ministry had issued draft rules dated April 12, 2018, to allow the remaining amounts of batches of vaccines which have been used in a clinical trial for marketable use after the entitlement of authorization in Form 46(now it's Form CT- 23) and manufacturing license in Form 28D. still, this draft rule has not been enforced till now. This draft rule should be enforced shortly to avoid destruction of life- saving vaccines.

Also perpetration of recommendations of inter-ministerial commission for reforming the medicine Regulatory Systems in India. The letter stated that on the directions of Prime Minister Narendra Modi, a high- powered inter-ministerial commission for reforming the medicine Regulatory Systems in India was constituted on May 11 last time under the chairmanship of also officer on special duty Rajesh Bhushan, who's presently the union health clerk. series of meetings of this commission was held starting May 2020.

Recommendations of this inter-ministerial commission should be enforced incontinently in line with the ease of doing business. Putting forward the following points with relation to necessary nonsupervisory reforms in the being Drug Regulatory system for your kind reference and intervention, which will take the vaccine assiduity of our country to new heights in the world.

The high minister's vision mentioning," It's a matter of great pride for all of us that because of our Prime Minister's vision about the nonsupervisory reforms, the vaccine assiduity of our country is growing veritably presto and under his global leadership, India has proved that as world leader in vaccine sector.

FDA: Accelerated Approval | Process | New Drugs | عملية الموافقة المعجلة لإدارة الغذاء والدواء على الأدوية الجديدة

 

The FDA has an accelerated approval mechanism for new drugs. Is accelerated FDA approval a good thing? Probably Yes. This mechanism of approval was put into place to help patients who suffer from certain serious diseases.

As the phrase suggests accelerated FDA approval involves a faster approval than for non-accelerated approvals. To get an accelerated approval sponsors must submit their application to the FDA. Before an application is accepted for approval, two major regulatory tests described below are applied. 

 

THE DRUG HAD TO TARGET SERIOUS CONDITIONS 

What is a serious condition? If you are a patient almost every disease would be a serious condition. The FDA has clarified this in a guidance document. 

This is a disease or condition which has significant impacts on a person's day-to-day ability to function or even die. 

Clinical judgment has to be made in determining whether a disease is serious or not. 

The judgment is based on the impact of the disease on factors such as the patients' survival and day-to-day functioning. In addition, an assessment is made on the likelihood that the disease will progress to a more severe condition if no treatment is provided. 

There are other three pathways for expedited approval of NDA which require establishment of serious condition. They include fast track, breakthrough therapy and priority review. 

All diseases that are life threatening qualify as serious illnesses but not necessarily for accelerated FDA approval as we will see later. Some will qualify for fast track, breakthrough therapy and priority review but not for accelerated approval.

 

THE DRUG HAD TO BE FOR AN UNMET MEDICAL NEED 

The term "unmet t Medical Need" is used to refer to a medical condition that does not have adequate treatment or diagnosis. It may be for treatment of cancer or a method for better and faster diagnosis of a serious illness. The application of the term "unmet medical need" could be quite broad.

The term "unmet medical need" could be used where there is no available appropriate treatment to the patients. Sometimes a new therapy may be available but unmet medical need may still exist such as when the new reduces the symptoms but not the serious outcome such as progressive disability or progression of the illness. 

 

WHAT THE SPONSOR SHOULD DO

Because many sponsors may want to use accelerated FDA approval, certain pre-qualification criteria have been put into place.

As the accelerated FDA approval application is based on surrogate endpoints. Sponsors should ordinarily discuss with the FDA of the intention to request for accelerated approval. 

The request would help the sponsor to choose the best surrogate endpoints during the clinical trials. Surrogate endpoints are endpoints other than clinical endpoints which take longer to determine for diseases that take long to show a clinical endpoint. 

For example, it might take long to show that a drug prolongs life. Prolongation of life is a clinical endpoint. Decrease in the blood in viral load such as in HIV would be a surrogate endpoint.

Surrogate endpoints include laboratory measurements and images among others. The use of clinical endpoints is however required in the confirmatory clinical trial reports.

By the time this application is being submitted the sponsor should be in a position to discuss the confirmatory clinical trials which should be in progress. 

Without evidence of these confirmatory trials the FDA may be reluctant to approve the requested accelerated FDA approval. The risk to patients is exposure to expensive drugs which may offer no clinical benefits. The sponsor must provide evidence for commitment to complete the pending confirmatory trials.

Does Canada have a similar program to accelerated FDA approval? The Canadian equivalence is called priority review. In this program the sponsor is encouraged to request for priority review status early. The sponsor will get a notice of compliance status with conditions after the application when the only data available is from surrogate end-points. 

The target review period is 200 days. Just as in USA, the sponsor has to submit confirmatory clinical trial data for full compliance without conditions.

 

 

 

 

Drugs: Lifecycle | Development | Retirement | دورة حياة الدواء: من التطور إلى التقاعد

Where do the medicines we take from chemists come from? How do the doctors know which drug is nice that disease? How the medicines really are able to cure a selected ailment they need been prescribed for? Do these questions come to your mind, whenever you get any medicine?

Come, allow us to today understand the medication development from the start. The development of drugs a Clinical Research and has different Phases. Phases of the clinical research are the steps of experiments with a health intervention in an endeavor to search out enough evidence for a process which the scientists think would be helpful in medical treatment.
The pharmaceutical study starts its journey from a drug design and drug molecule discovery which further progresses into animal testing so human studies to determine the drug's effectiveness.

Drug undergoes many trials- Preclinical, Phase 0, Phase I, II, III and IV. Sometimes combined trials are also undertaken to scale back the time of development, like Phase I/II and II/III.

Pre-Clinical Study

When the drug molecule is identified, it undergoes many in vitro (test tube or cell culture) and in vivo (animal) experiments. These experiments are conducted to grasp the preliminary efficacy, toxicity, and pharmacokinetics of the varied doses of the drug. Many drug molecules are designed at a time and these pre-clinical studies let the pharmaceutical companies decide which molecule includes a greater potential in further studies.

 

Design of the Studies:

Trials are always conducted by following the set of steps, called the protocol, developed by the researchers to search out the particular questions associated with the medical product. 

Information from the prior studies become the bottom for the researchers to develop research questionnaire and objectives:


Participant selection
Number of participants
Duration of the study
Controlled or not
How and what dosage are going to be given
What and when the information is collected
Review and analysis time


Phase 0 Study

It is also called micro-dosing trials; 10-15 human subjects are taken, and single sub-therapeutic doses are administered to collect the pharmacokinetic (PK) data of the drug. this allows the corporate to choose to travel or no select the further development of the drug, supported more relevant human data rather than animal data.

After the corporate decides to require the molecule of the drug forward in development, it'll must submit the info of its preliminary studies to the FDA called Investigational New Drug (IND) application filing.

 

Phase I Study

Also called First-in-man studies as these are the primary stage of human testing studies. These are the studies which are designed to work out the utmost dose which will be administered without showing adverse effects.

Contract Research Organizations (CROs) conduct such studies within the trial clinics where medical staff provides full-time attention to 2-100 healthy subjects enrolled for the study and collects the info.
These studies determine the security (pharmacovigilance), tolerability, pharmacokinetics (PK)and pharmacodynamics (PD) of the drug.  of phase I studies is dose-ranging also called dose escalation studies conducted in controlled clinics called Central Pharmacological Units (CPUs).

Usually, healthy subjects are hired but sometimes terminally ill patients like of cancer and HIV and also those that have already tried and did not improve on existing medications.

There are two divisions for phase I study:

Phase Ia: Single ascending dose

Phase Ib: Multiple ascending dose

 

Phase II Study

More than 100 diseased subjects are enrolled for a extended period study, to grasp the advantages of the drug together with its safety which has genetic testing. These studies are called as "Proof of Concept or Pilot" studies.

This is the phase when the drug's development can fail thanks to toxicity or but expected results.

Two divisions of this phase are:

Phase IIa: Pilot study, to see the clinical efficacy or the biological activity.

Phase IIb: Dose-finding study, to test the biological activity with minimal side-effects.

A combined trial determining the efficacy likewise as toxicity are Phase I/II trials.

Medicines, before coming into the market and sold over the counter, need to undergo a passage of development which is summarized during this article. Drugs are just a design or a molecule within the laboratory   which a scientist has found during the research. In the lab undergoes many tests in vitro and in vivo which then progresses into various phases of development based on the results shown by the drug molecule

The drug has to pass through Phase I, Phase II, Phase III, and after approval Phase IV trials.at any time if the expected results are not found or there is side effect then the whole development has to be paused or stopped either by the company or the regulatory authority under which it is to be or was approved.