Amy Ritter was Scientific Editor, BioPharm International.

Amy Ritter, PhD

In the quest for more targeted therapies and potentially more clinically efficacious drugs, bio/pharmaceutical companies are increasing their research and product development in biologics. Although the majority of this work is focused on monoclonal antibodies (mAbs) and recombinant proteins, progress is being made in specialized drug types. Antibody–drug conjugates (ADCs), which consist of a mAb chemically linked to a small-molecule therapeutic, are a niche class of drugs that offer promise, particularly as oncology drugs. In August 2011, FDA approved Adcetris (brentuximab vedotin), codeveloped by Seattle Genetics and Millennium Pharmaceuticals (now part of Takeda Pharmaceutical), making it only the second ADC approved by FDA. With the approval of Adcetris, a drug for treating Hodgkins lymphoma and systemic anaplastic large-cell lymphoma and with a number of ADCs in clinical development, the key question is whether ADCs will be able to fill a role in biopharmaceutical development. 

(COMPOSITING BY DAN WARD. IMAGES: NICK KOUDIS/INGRAM PUBLISHING/GETTY IMAGES) 

Adcetris consists of three parts: the chimeric IgG1 antibody cAC10, specific for human CD30, the microtubule-disrupting agent monomethyl auristatin E (MMAE), and a protease-cleavable linker that covalently attaches MMAE to cAC10 (1).  Before the approval of Adcetris this year, the only other ADC approved by FDA was Mylotarg (gemtuzumab ozogamicin), approved more than 10 years ago in 2000. The drug, an anti-CD33 mAb conjugated to the cytotoxin calicheamicin, was developed by Wyeth (now part of Pfizer) and was granted accelerated approval in 2000 but was voluntarily withdrawn by Pfizer in 2010 because a required Phase III trial failed to demonstrate a survival advantage for Mylotarg plus chemotherapy compared with chemotherapy alone. Despite this setback, there are several ADCs currently in development, with more than 15 in Phase I development and several compounds from Roche and Pfizer in late-stage clinical trials. In the decade that has elapsed between the first ADC approval and the second, advances in the understanding of cancer biology, lessons learned from the development of mAbs as therapeutics, and better methods for linking small molecules to mAbs have coalesced to advance ADCs into the forefront of new therapies. 

The most active area of development for this class of therapeutics has been oncology, where a mAb serves to target the therapy to cancer cells while a potent small-molecule chemotherapeutic provides the cell-killing efficacy. Both mAbs and small-molecule chemotherapeutics are used individually as cancer therapies, but an ADC is designed to overcome the limitations of each.  MAbs are highly specific, but as therapeutics have demonstrated only modest efficacy and often are used in combination with a conventional chemotherapy.  Chemotherapeutics are highly toxic, but nonspecific, and so suffer from poor side-effect profiles and dose-limiting toxicities. In combination, the ADC serves to keep the chemotherapuetic bound until it reaches the cancer cell, thereby limiting its ability to interact with nontargeted tissues and therefore limiting nonspecific toxicity (2).  

The concept of an ADC is not a new one, but creating a clinically successful one has been challenging.  For the therapeutic to work well, each of the parts—the antibody, the toxin, and the linker that holds them together—must be carefully considered. 

In general, mAbs as therapeutics are selected to have high affinity for the targeted antigen and high selectivity.  Other desirable properties in an antibody include long circulation times, immune-effector functions, and tumor-suppressing activity (2). When choosing the antigen, it is important that it be expressed at high levels in the tissue of interest to maximize the amount of ADC bound by the tumor, but at low levels elsewhere in the body to minimize off-target toxicity. Moreover, it is thought that internalization of the ADC is important for its effectiveness.  Many of the chemical-linking strategies used to construct ADCs rely on conditions found inside a cell, either in the cytoplasm or in the lysosome, to release the active agent (3).  

In some instances, developers have been able to leverage experience gained through the development of mAb therapies to create their ADC. Trastuzumab emtansine (T-DM1) is an ADC in Phase III, which combines trastuzumab, (Herceptin), which targets human epidermal growth factor receptor 2 (HER2) receptors in breast and stomach cancer, with a maytansine derivative DM1, a small-molecule cytotoxin that binds to tubulin to prevent microtubule formation, through a nonreducible bis-maleimido-trixyethylene glycol linker (4). Trastuzumab was developed by Genentech (now part of Roche) and was approved by FDA in 1998 for use in women with metastatic breast cancer who have tumors that overexpress the HER2 protein. The maytansine derivative DM1 and linking technology were developed by ImmunoGen. In the case of the ADC trastuzumab emtansine, developers were able to use a target that had already been validated and a well-characterized antibody with a known safety and efficacy profile as the starting point for an ADC. 

Choosing the right cytotoxic small molecule

The earliest versions of ADCs used stand-alone chemotherapeutics such as doxorubicin, methotrexate, or vinca alkyloids as the cytotoxic arm of the conjugate. Clinical-trial results using these ADCs were disappointing, and it is thought that part of the problem was the relatively low potency of the toxins used (2). The newer classes of cytotoxins are at least 100-fold more potent than the older molecules, with 

There are only a few major chemical classes of toxins being explored. They can be divided into two types, those that cause damage to DNA and those that interfere with tubulin polymerization.  Calicheamicin, used in Mylotarg and in Pfizer's inotuzumab ozogamicin, an ADC in Phase III trials, binds to the minor groove of DNA and induces double-strand DNA breaks that result in cell death. Duocarmycins, isolated originally from 

 bacteria, are DNA minor-groove binding alkylating agents (2). Fully synthetic duocarmycin derivatives are being used by the biopharmaceutical company Syntarga (acquired by the pharmaceutical company Synthon in June 2011) for ADC constructs (see sidebar). 

Microtubule disruptors are represented by two major classes: maytansinoids and auristatins. Maytansinoids are deriviatives of maytansine, a natural product originally isolated from the shrub 

. ImmunoGen has focused on development of this class of cytotoxic small molecules and associated linker technologies and has been devloping maytansinoid ADC compounds singularly and in partnership with other companies. In addition to trastuzumab emtansine, which is being codeveloped by Roche and ImmunoGen, another example of a maytansinoid ADC being developed by ImmunoGen is the company's IMGN901, which uses the maytansinoid DM4. Auristatins are synthetic analogs of dolostatin 10, a natural product derived from a marine mollusk, 

. Like the maytansinoids, auristatins are microtubule disruptors. Millennium and Seattle Genetics' ADC Adcetris is a conjugate of an anti-CD30 mAb to monomethyl auristatin E (MMAE). Seattle Genetics focuses on the development of auristatin-conjugated ADCs, using the auristatins MMAE and monomethyl auristatin F (MMAF) and proprietary linkers.  

Developing the right linker and method of attachment is a crucial part ADC development. "Many areas around the process have improved, however, the linker strategy for ADC manufacturing and their application has certainly contributed perhaps the most in moving the field forward," says Grant Boldt, director of business development at the CMO SAFC. The creation of linkers that are stable in circulation but labile upon binding of the ADC to its target has resulted in the current generation of ADCs having better stability and lower systemic toxicity than earlier ADCs, according to Boldt.  Early versions of ADCs, including Mylotarg, suffered from instability while in circulation. The linkage between the mAb and the cytotoxic small molecule were destroyed by endogenous proteases in the blood, and the premature release of the cytotoxin resulted in side-effect profiles similar to that of an unconjugated chemotherapeutic. The current generation of linkers is more resistant to degradation in the blood while still allowing release of the payload at the target. Choice of a linker is influenced by which toxin is used, as each toxin has different chemical constraints (6).  

Linkers can be divided into two broad categories: cleavable and noncleavable. Cleavable linkers rely on processes inside the cell to liberate the toxin, such as reduction in the cytoplasm, exposure to acidic conditions in the lysosome, or cleavage by specific proteases within the cell.  Noncleavable linkages require catabolic degradation of the conjugate for release of the cytotoxic small molecule.  The released cytotoxic small molecule will retain the linker and the amino acid by which it attached to the mAb.  Importantly, both classes are designed to release the cytotoxic small molecule only after the ADC has reached the interior of the cancer cell (2).  

There are a limited number of chemical moities on proteins, including mAbs, that are available for chemical modification. Linkers can attach to the mAb through the amino groups of lysine residues, or by the thiol groups on cysteine residues. Attachment is a pseudorandom process:  in theory, any of the targeted amino acids within the mAb, either cysteine or lysine, can be modified (3). According to Boldt, the conjugation reaction results in a heterogeneous mixture of conjugated species, but the proportion of each species in the mixture is reproducible from batch-to-batch and quantifiable. 

Producing the ADC requires both biologic-based and small-molecule manufacturing. "One of the biggest challenges in manufacturing ADCs is controlling all the components that go into the final conjugation step," says Boldt. "Namely, the three main components that make up an ADC (e.g., antibody, linker, and payload) are all manufactured in very different ways. For example, it is not uncommon for these components to be manufactured by synthetic chemistry and mammalian cell culture. Thus, there presents a challenge in ensuring all these components have been manufactured under cGMP, and subsequently  bringing them all together to generate the final ADC under cGMP, as well." 

The biologics portion of the ADC and the high-potency API require very different handling methods, and manufacturers must make sure that handling requirements for both are met.  "It is imperative that manufacturers emphasize the protection of the product from workers as well as the protection of workers from the product," says Jason Brady, head of business development, conjugates and cytotoxics at the CMO Lonza. Clinical ADC manufacturing is executed in an aseptic biological manufacturing environment to protect the product from contamination, explains Brady.  Once conjugated with the high-potency API (which is manufactured in a high-containment environment), the resulting ADC also is handled under high-containment conditions. The level of containment is determined by occupational exposure limits for the high-potency API and resulting ADC.  The environment must provide manufacturing personnel with isolation from cytotoxic chemicals in the occupational exposure range of 5 ng/m3 of air. Also important is that facility design includes design of equipment and process contact surfaces that permit clean-in-place and steam-in-place to remove minute traces of residual drug contamination during both interbatch and product changeover cleaning, according to Brady. 

As ADCs advance in the clinical pipeline so does the technology to manufacture ADCs to control certain product and process conditions. "New technology that can limit the heterogeneity of ADC products is something that will be important in the future," says Brady.  "ADCs made via current technologies are heterogenous mixtures. Heterogeneity can be controlled and measured by robust and reproducible manufacturing processes and proper analytics, but new technologies will likely emerge to influence and improve ADC manufacturing," he explains. Some fraction of the finished drug product consists of unconjugated antibody. The remaining portion of the finished drug product contains conjugated antibody with a variable number of the cytotoxic small molecules conjugated at different sites on the antibody. Controlling the number and location of cytotoxic molecules conjugated to the antibody is being pursued as a means to create a more uniform product and as a way of being able to explore structure–function relationships by varying the site of attachment of the cyotoxin. 

One strategy for controlling the site of attachment has been developed by researchers from Genentech, a member of the Roche Group. They describe precise site-specific conjugation of human IgG1 to MMAE by replacing Ala114 at the junction of the CH1 and the variable heavy-chain domain with cysteine to create an engineered antibody called a THIOMAB. This site was chosen because it does not participate in antigen binding or effector functions. According to Jagath Reddy Junutula, senior scientist at Genentech, the process for creating a THIOMAB differs only slightly from that of a conventional mAb. The THIOMAB is subjected to partial reduction to remove cysteine and glutathione adducts. The partial reduction also breaks interchain disulfide bonds, which must be reformed by a reoxidation step. After reoxidation, the engineered cysteine residues are available for conjugation. 

Genentech researchers used this process to conjugate MMAE to  a THIOMAB version of an antibody against MU16, a cell-surface protein expressed in ovarian cancer cells. The THIOMAB conjugate was shown to be homogenous and to contain a single drug molecule attached to each heavy chain, for a total of two MMAE molecules per ADC. The THIOMAB–MUC16 was found to have comparable efficacy to a conventionally produced ADC and to be better tolerated in two preclinical species (7).  In a subsequent study, a different cytotoxin, DM1, was conjugated to a THIOMAB version of trastuzumab. Results were similar, with the THIOMAB T–DM1 displaying comparable efficacy and better tolerability in preclinical species than its conventionally produced counterpart (8).  

According to Junutula, the reoxidation step is the only thing that distinguishes manufacture of a THIOMAB drug conjugate from that of a conventional ADC. "We can make up to grams scale without any difficulty.  And the results are huge—you have a homogenously conjugated cytotoxic drug to the antibody," he says. 

While the THIOMAB uses the substitution of one amino acid for another to control the site of conjugation, several groups are working toward incorporating nonnatural amino acids into the mAb for to control the site of conjugation and also to provide an expanded repertoire of functional groups that could be used for linker chemistry. The biopharmaceutical company Ambrx has developed expression systems in 

, yeast, and Chinese hamster ovary (CHO) cells that can be used for such substitutions and which can be scaled up to volumes required for commercial manufacturing. Ambrx's expression systems contain engineered transfer RNAs that will read through a stop codon called amber, as well as engineered tRNA synthetases that will aminoacylate the orthoganal tRNA with an Ambrx nonnatural amino acid. The expression system will insert a nonnatural amino acid whenever the amber stop codon is encountered (9).  

Sutro Biopharma, a provider of protein-synthesis technology, also is developing a platform for introducing nonnatural amino acids, but in a cell-free translation system that is reported to be scalable to commercial production volumes (10). The system is based on an extract of 

, and because it is an open system, the tRNA charged with a nonnatural amino acid can be added directly to the reaction mix as a reagent.  

The future of ADCs in the biopharmaceutical market will ultimately depend on their clinical success. Companies and researchers are seeking to meet that challenge by optimizing the selection of all the components in the ADC—the antibody, linker, and cytotoxin—and successfully combining manufacturing techniques for both high- potency APIs and biologics. ADCs are sometimes described as armed antibodies, and their cytotoxic components as warheads. Whether ADCs will prove to be an effective weapon against cancer or other diseases has yet to be seen as more are tested in the clinic. 

 1. FDA, "Label for Adcetris, BLA 125338," FDA 

Articles

Creating a successful antibody-drug conjugate requires careful selection of the drug, antibody, and linker.

Antibody-Drug Conjugates: Looking Ahead to an Emerging Class of Biotherapeutic

The Government Accountability Office (GAO) issued a 

 recommending that FDA’s ability to respond to drug shortages be strengthened. The report was released in conjunction with a Senate hearing before the Committee on Health, Education, Labor, and Pensions on Dec. 15, 2011, on the subject of drug shortages. The report reviews trends in prescription drug shortages, identifies the reported causes of selected shortages, describes FDA’s response to drug shortages, and evaluates the extent to which FDA can protect public health through its response to drug shortages.

According to the report, FDA responds to drug shortages by taking actions to address the underlying causes of the shortage and to enhance availability. The report notes that when informed in advance of a potential shortage, FDA has increasingly been able to prevent shortages from occurring. But the report concludes, “FDA is constrained in its ability to protect public health from drug shortages due to its lack of authority to require manufacturers to report actual or potential shortages to the agency or the public, or to require manufacturers to take certain actions to prevent, alleviate, or resolve shortages. As a result, the agency’s approach to managing drug shortages is predominately reactive.”

The GAO recommends that Congress consider establishing a requirement for manufacturers to report any circumstances that could affect the supply of their drugs. In addition, GAO recommends that FDA enhance its ability to respond to potential shortages by developing an information system to manage data about shortages.

The Government Accountability Office issued a report recommending that FDA's ability to respond to drug shortages be strengthened. The report was released in conjunction with a Senate hearing before the Committee on Health, Education, Labor, and Pensions on Dec. 15, 2011, on the subject of drug shortages.

GAO Recommends Strengthening FDA's Ability to Respond to Shortages

AstraZeneca entered into an agreement to acquire Guangdong BeiKang Pharmaceutical, a privately owned generic-drug manufacturing company based in Guangdong province, China, for an undisclosed amount. Guangdong BeiKang Pharmaceutical’s portfolio includes injectable medicines used to treat infections. Upon completion of the acquisition, AstraZeneca will be responsible for the manufacture and commercialization of these medicines. The deal is contingent upon approval from the Ministry of Commerce in China and is expected to close in the first quarter of 2012.

AstraZeneca first established a presence in China in 1993 and has invested around $500 million in China since that time, according to a company 

. In October 2011, AstraZeneca invested $200 million in a new manufacturing facility located in the Jiangsu province that will produce intravenous and oral solid medicines for the company’s growing business in China. The acquisition of Guangdong BeiKang Pharmacuetical accelerates AstraZeneca’s strategy, which aims to increase the accessibility and affordability of medicines for wider patient populations that are currently underserved.

“AstraZeneca continues to invest in the key emerging markets such as China where the combination of growing populations, elevated levels of chronic diseases, and increasing income are driving demand and expectations for better healthcare treatment,” said Mark Mallon, president of AstraZeneca’s Asia-Pacific region, in the press release. “Our new acquisition further underscores our intention to serve the health needs of Chinese patients through our innovative medicines and, increasingly, high-quality branded generic treatments that are locally produced to global standards.”

AstraZeneca Plans $200-Million Manufacturing Plant in China

AstraZeneca entered into an agreement to acquire Guangdong BeiKang Pharmaceutical, a privately owned generic-drug manufacturing company based in China, for an undisclosed amount. Upon completion of the acquisition, AstraZeneca will be responsible for the manufacture and commercialization of these medicines.

AstraZeneca to Expand Presence in China

On Dec. 6, 2011, FDA announced that a public meeting will be held on Dec. 16, 2011 to discuss recommendations for a user-fee program for biosimilar biological products for fiscal years 2013–2017. Under the Biologics Price Competition and Innovation Act of 2009, FDA must publish the 

recommendations for a biosimilars user-fee program

, and provide a period of 30 days for the public to provide written comments on the recommendations. FDA is also required to hold a meeting at which the public may present its views on such recommendations.

The recommendations that will be presented were formulated after a period of consultation and negotiation with members of industry and public stakeholders that occurred between June and September 2011. Stakeholders were asked to consider how a biosimilar fee program should differ from the structure outlined under the Prescription Drug User Fee Act (PDUFA), and whether fees should be used to support postmarketing safety studies.

According to the FDA release, the proposed fee structure is similar to the PDUFA program, in that fee revenues would be used to support marketing applications, manufacturing, and products. In addition, it provides for fees collected earlier in the development process to support a series of biosimilar product-development meetings between sponsors and FDA. As outlined in the FDA release, four types of fees are proposed:

The release also contains an outline of proposed review performance goals and procedures. FDA aims to review 70% of original biosimilar biological product applications within 10 months of the receipt date. A 

 of the proposed goals and procedures for the biosimilars user fee program can be found on FDA’s website. 

Concerning the draft performance goals, Pharmaceutical Research and Manufacturers of America (PhRMA) vice-president Sascha Haverfield-Gross said in a 

, “The performance goals letter published today demonstrates FDA’s commitment to a science-driven approach for biosimilars. The letter provides for FDA and sponsor meetings for the substantive review of biosimilar development plans. It also includes a special protocol assessment mechanism for clinical trials intended to establish biosimilarity and/or interchangeability with the innovator biologic product. This provision will help to ensure that clinical trials are designed to thoroughly assess the safety and efficacy of biosimilar medicines, in accordance with the FDA’s high regulatory and scientific standards.”

On Dec. 6, 2011, FDA announced that a public meeting will be held on Dec. 16, 2011 to discuss recommendations for a user fee program for biosimilar biological products for fiscal years 2013–2017.

FDA Announces Public Meeting to Discuss Biosimilar User Fees

The economic and financial crisis that thundered through the world economy in 2008 still rumbles on today. The downgrade of the US debt rating in August 2011, along with the economic chaos that has taken over the European Union in recent months, have done little to lend confidence to the bio/pharmaceutical market. When analyzing data from 

 2011 annual employment survey, readers' outlooks are positive with regard to job security and business growth for 2012. Approximately 64% of respondents feel that their jobs will be secure in 2012, while 82% believe 2012 will bring improved business conditions or, at the very least, not decline. 

In last year's survey, everyone was riding the employment roller coaster—11.3% of respondents lost their jobs but salary rises were given to those lucky or smart enough to remain in employment. This year, 7.2% left jobs involuntarily following restructuring, but many other indicators remain relatively unchanged, with 59.4% experiencing a salary increase. The median salary of all respondents rose from $102,500 in 2010 to a median  of $103,100 for 2011.  

At the end of 2010, the majority of survey respondents thought that business within the bio/pharmaceutical industry would improve in 2011, but given the enormity of global economic worries, it's no surprise that a recovery has been somewhat delayed.  

Given the tone of mass media this past year, most respondents have probably had cause to consider just how secure they are in their current roles. But the results from the 2011 survey are positive. As noted, 64% of respondents "agree strongly" or "agree somewhat" that they are secure in their current job (see Figure 1). To put this into context, insecurity ran high at 53% in 2010—US respondents were above the average at 55.3%—so there is a marked improvement. It is interesting then that, when asked to compare job security to last year, 40.9% claim they feel less secure today than in 2010 (men somewhat less secure at 44.8% than women at 33.3%). Nevertheless, 33.6% of you would consider moving to another position based solely on improved job security, with another 52.9% considering it an important criterion, making it  clear that security is still an issue of concern.  

Figure 1: Respondents indicate to what extent they agree with statements about their current position and company. 

Breaking the data down by organization type, contract manufacturers and service providers offer slightly more security (68.9% agreed their job was secure) than generic or traditional bio/pharmaceutical companies (64% and 63.8%, respectively) in a pattern that reflects last year's survey, although groupings are closer for 2011. The pattern is somewhat reversed when respondents discuss whether they were likely to leave their job involuntarily in the coming year; 28% of respondents working for generic-drug firms agreed, as compared with 21.5% in traditional pharma companies and 25% in contract organizations. Geographically, things get a little more interesting; Europe (East and West) trails in job security with 58.7% of respondents feeling safe, US and Canada match the total figure at 64.5%, but for the rest of the world (of which 54.5% is made up of India) job security sits at a very high 84% (see sidebar, "Emerging economies," for  more details about India's bio/pharmaceutical employment sector). 

Only 21.6% of all respondents agreed that leaving their job involuntarily was likely, but what about moving on to new pastures voluntarily? A hefty 66.5% of respondents "disagree strongly" or "disagree somewhat" that they will leave voluntarily (33.5% were in agreement), so many are either satisfied at work, or mindful that the job market has seen better days. Once again, location plays an important role in this opinion. In North America, the figures follow the general trend (because of the survey weighting), with 30.5% of respondents agreeing that they are likely to leave their job voluntarily. In Europe however, the figure ramps up to 38%, and for the rest of the world, almost half "agree strongly" or "agree somewhat" with the statement. Given that these figures are at odds with job security, there must be significantly more powerful drivers for job satisfaction.  

According to this year's responses, salary is surprisingly not a pillar of job satisfaction but is important. Only 34.3% of respondents feel they are paid fairly for their level of expertise, despite 59.4% of respondents receiving salary increases in 2011. Rather, the majority (46%) feel that they are paid at the low end of the scale but within market value or simply not paid the going rate (19%)(see Figure 2). Location also seems to have little part to play with salary satisfaction, with similar responses given across the world.  

Figure 2: Respondents indicate their level of salary satisfaction. 

When it comes to salary increases, Europe seems to have the least generous employers, with only 50% of respondents seeing an increase in 2011 and a relatively high 12% witnessing decreases in salary. Compare these percentages with North America's 61.7% of respondents who had an increase and 7% of which had a decrease this past year, and the rest of the world which had 69% of respondents indicating a salary increase (and only 6.9% experiencing decreases).  

Although respondents may not get paid what they believe they deserve, they do feel respected and needed by their employers. Three quarters of respondents agree (either strongly or somewhat) that their work is fully valued by their employer, up from 64.6% in 2010 (see Figure 1). This feeling is particularly strong in traditional bio/pharmaceutical companies (80.8%) compared with generic-drug firms (64.7%) and contract organizations (70.5%); it seems some headway has been made for contract organizations, which were struggling at the bottom of the pile last year with only 58.4% of respondents feeling valued. It could be that ever-stronger relationships between CMOs or CROs and partner companies have helped foster a sense of value among all employees working on projects together. Following the trend from last year, men feel slightly more valued than women (at 76.1 and 73.3%, respectively). 

So, aside from feeling valued, what other factors help bio/pharmaceutical employees face the early alarm clock every morning? As in 2010, "intellectual stimulation" is the number-one driver, with 61.9% of respondents considering it an important contributor and 27.3% indicating that it is a main source of satisfaction. In fact, this is the top answer regardless of location. The "chance to work on challenging projects" is a close second, with 59.5% citing it as an important factor, and a 28.9% indicating that it is their main reason for going to work. Improved work–life balance, job security, better salary, and benefits fill out the rest of the top of the list in descending order of importance (see Figure 3).  

Figure 3: Resondents indicate the importance of different factors in job satisfaction (multiple responses were allowed). 

One notable difference this year compared with 2010 is that similar job satisfaction results are produced irrespective of location, type of organization, and gender. This harmony is also the case when considering the factors that weigh in the decision to change jobs. Thirty-seven percent of all respondents say they would change jobs for an improved work–life balance alone; similarly, professional advancement (36.6%), salary (33.2%), job security (32.6%), and intellectual challenge (31.3%) are all strong deciding factors (see Figure 4). Changing tact slightly, when asked which sole factors would make respondents quit, 38% cite low pay. Discrimination also ranks highly as a reason to leave a job (34.4%). However, the latter response may be hypothetical considering that 78% of respondents say they have not experienced discrimination in their current job. Surprisingly, 41% of all respondents say that restructuring or the threat of a restructure has no impact on feelings about work. Perhaps this is because, of the 59.7% of you who have been through a merger, acquisition, downsizing or restructuring, 42% saw no significant effect and 39.8% saw only a change in job responsibilities. Therefore, just 18.2% left jobs voluntarily or otherwise.  

Figure 4: Respondents indicate the factors that would entice them to leave their current position (multiple responses were allowed). 

In conclusion, respondents want to be paid more in better jobs with more benefits, while enjoying a reduced workload and suffering from less stress—no real surprises there. Looking forward to 2012, a very positive 50.9% of respondents think that their company's business will improve in 2012 (only 17.9% expect a decline). As for the general outlook of the bio/pharmaceutical industry, once again, the results are positive with 72.6% predicting that business will improve. However, 24.2% believe growth will only occur overseas in 2012. Only 11.3% expect no significant change, leaving 16.1% of respondents lying awake at night worrying about decline.  

As bottles are uncorked and glasses raised on December 31, toasts should be made to a prosperous, healthy and bright 2012. 

Readers react to the economic turmoil of the past year and look longingly forward to 2012.

The Employment Outlook Brightens

The economic and financial crisis that thundered through the world economy in 2008 still rumbles on today. The downgrade of the US debt rating in August 2011, along with the economic chaos that has taken over the European Union in recent months, have done little to lend confidence to the bio/pharmaceutical market. When analyzing data from Pharmaceutical Technology's 2011 annual employment survey, readers' outlooks are positive with regard to job security and business growth for 2012. Approximately 64% of respondents feel that their jobs will be secure in 2012, while 82% believe 2012 will bring improved business conditions or, at the very least, not decline. 

This article was also published in our US sister publication 

The results from our employment survey are in.