Pushpavalli Krishnamurthy: Elevating Pharmacopoeia Standards at Ingredion

Pharma Now: Hello. Welcome to Pharma Now, Ms. Krishnamurthy. You're currently the Global Head of Regulatory Affairs at Ingredion. Can you share how you achieved such a prestigious position, and what exactly your role entails?

Ms. Krishnamurthy: Thank you for inviting me to speak at Pharma Now. It is my pleasure to talk about the regulatory profession and its importance in the pharma industry and navigate the regulatory principles of how regulators are valuable to humanity. I am privileged to be able to discuss this.

I’ll give you a brief about me: I am Pushpavalli Krishnamurthy. I am from Southern India and currently living in Bangalore. I have a Master's in Pharmacy. I started as a quality control (QC) and quality assurance (QA) chemist. Then, I moved to regulatory affairs, explored global international regulations, especially biosimilars, and moved to a South Africa-based multinational corporation (MNC). I was working on a new profile variation file—biosimilars with new formulas, especially on biologics license application (BLA) and new drug application (NDA) for European registration. 

After a few years, I became a portfolio lead for a generic prescription drug in the women's portfolio. The company already had a genetic product register, with 1000+ products registered and almost 150 products in the women's health portfolio. Our back office is located in Bangalore, and our front office is located in the midland, South Africa. The team in Bangalore supports all global variations, and it has provided me with all the knowledge from raw material supply to international marketing. I learned about changes and how a formula can be kept alive. I learned a lot from all the work I delivered.

Then, I moved to a startup company in Chennai. So, from an MNC to a startup, it was a huge change. The Managing Director of that company insisted on my support as he had invested a lot. It was very new for me. Then, I was on a board at Sunglow Life Sciences, which has a plant for producing over-the-counter (OTC) medicine and therapeutic goods administration (TGA). When I joined that company, they were making 7 products on that site. By the time I left, we had received approvals for 150 product licenses, and the products had a presence in 20+ countries globally. I was instrumental in developing the regulatory principle for Sunglow. Because of that, I also had an opportunity to oversee national regulations and work with the Central Drugs Standard Control Organization (CDSCO) and the Drug Controller General of India (DCGI).

Pharma Now: Having worked with national and international agencies, I'm sure you've seen many differences. In your opinion, which experience was better: working with international agencies or national agencies?

Ms. Krishnamurthy: This is a very tricky question, but I would say both are important. I had practical knowledge and knew about the principles of CDSCO theoretically, but when it came to practicality, I realized that I was unaware of international tenets. 

Whenever I had a chance, I had questions, which was considered arrogant. Still, after some time, it was appreciated because we got insights into what was needed to adhere to international regulations. Putting in a plan related to the Drug Law of India was very beneficial for us.

I have seen that the CDSCO has taken many initiatives in the last 6 months. I had the opportunity to attend programs and express the need to upgrade their guidelines. I gave my insights into what is needed for India's stability guidelines in one of the meetings I attended in 2019.

Pharma Now: I can only imagine how big of an opportunity that was. I've also read similar reports, that the CDSCO has taken on more initiatives in recent years. Have regulatory agencies become more active after COVID-19?

Ms. Krishnamurthy: The Drug Control Department is evolving and revising its guidelines, and its strategies have changed a lot. Now, we have separate policies for medical devices, which have bloomed in the last five years, with revisions and categorizations for import regulations. The Committee is keeping track of listed drugs that need to be upgraded. Hence, there have been a lot of changes in the Indian pharma industry regulations. 

Another important thing is that label claims. The label plays an important role. The Food Safety and Standards Authority of India (FSSAI) released a statement that all food companies must provide a proper label, and misclaimed labels will not be approved. They make it necessary for manufacturers to provide adequate labels. This is just an example. In the pharma industry, this movement happened 5 years ago. According to the Drug and Cosmetic Act, there are almost 12 schedules for drugs and cosmetics, so they strictly include more substantial label compliance. 

Our government is educating the industry. We need to follow how the United States Food and Drug Administration (US FDA) has labelled compliance in a separate chapter. Every country has a pharmacopoeia, which plays a significant role in the drug market. The active pharmaceutical ingredient (API) and excipients should follow the United States Pharmacopoeia (USP). They need to justify the reason and methodology for that dossier if another pharmacopoeia is used.   

The manufacturers know API, British Pharmacopoeia (BP), and USP recommendations. In India, we use ingress protection (IP)-grade materials. Few manufacturers follow the same standards. For example, if they need magnesium stearate, they can procure USP, BP, or IP grade. They have to keep a record of the standard of the obtained raw material and test the standard. This is done so that they don’t compromise on quality and efficacy while manufacturing medicines, whether domestic or international. This is important, it's where regulations come into action. It is not just about giving pharma companies a dossier (pharmacopoeia) to follow. The dossier needs to provide proper guidance to management, supply chain, and analytical development teams. 

When we talk about the API, we think about the quality, but when we discuss excipients, we think about cost efficiency. This needs to change. There is a way in the regulation to achieve both API and excipients cost-efficiently. The regulatory body needs to get involved in management reviews, which is not only for supply chain management and R&D but also in all practices, which will lead to cost reduction.

Pharma Now: So you mean to say, that regulatory guidelines are not limited to documentation but also include good practice.

Ms. Krishnamurthy: Yes, it is not just documentation, it's a principle. Regulatory guidelines are not limited to the dossier. They provide regulatory standards, and quality and regulations are not separate. 15 years ago, there was no regulatory department.

I was in the QC-QA department when I worked in a contract research lab in Chennai. I used to do the RM sampling in the morning, improved sampling in the afternoon, final product sampling in the evening, and report all results the next day. So, at that time, I had the involvement, dedication, and an owner mindset at every step. You'll never grow bold if you think it is not your job. You need some key principles: innovation, ethical standards, confidence in your ideas, resilience, and an owner’s mindset.

Pharma Now: I agree completely. In the pharmaceutical industry, the owner's mind is essential. Most companies face the same challenges because people leave early, attrition is very high, and people are unwilling to take responsibility. 

Ms. Krishnamurthy: Having an inclusive culture is another critical thing for companies. When employees exhibit this type of behavior or characcter and the management welcomes it, a good relationship is formed. 

Pharma Now: Yes, as a Global Head of Regulatory Affairs at Ingredion, what does your role entail?

Ms. Krishnamurthy: When I was working as a Drug Product Regulator, I resigned from my job to take care of my family. Then, I worked as a freelance consultant in the cosmetic and excipient industry. At that time, Ingredion India Private Limited was attempting to meet the import regulations for excipient profiles. When I provided them with a regulatory strategy, they were inspired and took me on board as a Global Regulator. At that time, they wanted to become a manufacturer in India and transfer technology from the US to India. That was the right time. I was on board and became a Global Regulatory Leader for Ingredion’s pharmaceutical business.

Pharma Now: How do regulations impact an existing company in the pharmaceutical space?

Ms. Krishnamurthy: Regulations play wonders in an excipient industry. Ingredion India Pvt, Ltd. changed its name from an import company to a manufacturing company. I supported them with technology transfer, helped them get qualified for the excipient production industry, and implemented the Good Manufacturing Practices (GMP) required in the pharmaceutical excipient manufacturing unit. I educated them on the terms to follow among all regulations. I made changes including additional test parameters and making limits and operational standards more stringent. This information and change helped them attain a manufacturer's status.

Ingredion India also acquired Amishi Drugs & Chemicals (AD&C), expanding their portfolio from starch to other specialty chemicals. It also has a joint venture with Mannitab Pharma Specialities, exclusively focusing on advanced technology spray drying. Ingredion is the first company to manufacture domestic and export spray-dried mannitol. We are the first player in the market. Usually, spray-dried mannitol is imported into India from South Africa or Malaysia. 

Now, India and China play a major role in manufacturing generic drugs. As an excipient regulator, my major role focuses on specifications we need to follow to meet all global standards, as we are a global supplier. Ingredion has a presence in 120 countries. For excipients, we have four production plants in the USA, other plants in Europe and Germany, two plants in South Africa, as well as five production plants and three contract manufacturing units in India. In China and Thailand, we are focusing on expanding our portfolio.

My primary responsibility is to study all pharmacopoeia standards and compare methods that can be used to achieve the highest standards. I set the specification limit for achieving the highest standards. Along with that, I also set quality parameters for process testing. I also oversee designing specifications and product quality, designing the QMS practices, and label compliance to meet all individual global requirements. What should be the procurement order, and what type of standards are needed to minimize the product quality risks? To support our customer, which risk assessment will be beneficial for our customer? It’s my job to figure out the answers to these.

For instance, if a drug has a high risk of elemental impurity, it is always a headache for drug product manufacturers if the excipients or API have more elemental residue content. This directly affects the drug quality. So, in Ingredion, I have created strong guidelines called risk assessments for the final excipient. I implemented the guidelines according to the protocol, including how many parameters need to be tested, the criteria and method to test these parameters, and how to interpret results as a uniform report for global customers. 

We release the excipient information package, which is a dossier. Ingredion is the parent company of Ingredion Pharma Solution. We maintain 40 pieces of documentation for regulatory requirements. The company also provides a drug master file (DMF) registration to Canada and the US. For some countries, the drug product dossier needs to be reviewed by the regulator. 

I manage three different portfolios. One is the registration portfolio, in which I look after the DMF filing variation, filing query response, annual report filing, input regulation, and custom clearance The second is addressing customer requirements. It includes developing an excipient, creating information packages in line with current regulations, updating versions of information packages, addressing each customer question regarding quality regulations, managing audit records, creating quality agreements, and risk assessment. 

These are the two ends: a rapid response team for customers and a documentation team for an excipient information package and DMF registration. I also participate in regulatory intelligence, where I associate with health authorities in the forum, keeping the team updated about changes needed in our plans.

Pharma Now: I see that you wear a lot of hats in this role. One thing that I noted from your profile and experience was that you’ve spent a significant portion of your career in regulatory departments. What does the future look like for the Indian regulatory industry–especially for young aspirants?

Ms. Krishnamurthy: There are many areas of regulation, such as regulatory registration, intelligence, documentation specialist, and information management. Many companies, like IQVA, act as regulatory consultants for pharma companies. Many global players outsource their regulation tasks to regulatory consulting firms. 

India has an excellent talent pool of pharma students. This is the reason why Ingredion, a US-based company, is investing and transferring its production plant from the US to India. India has become the centre of excellence for pharma, not only in production and operation but also in regulatory matters. 

This is because the Indian government is also coming forward and accepting and understanding the global regulatory knowledge of domestic examples from previous years. Indian Pharmacopoeia has become a harmonized Pharmacopoeia. This evolving and emerging trend is the reason for India's growing talent pool.

Pharma Now: I agree that India’s growing talent pool will definitely boost our industry. Unfortunately, our time is up, Ms. Krishnamurthy. Thank you for taking the time to speak with us at Pharma Now. It was our pleasure to have you.